| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :1.1182424 |
| We show that ARF interacts with c Myc independently of MDM 2 or p 53 . 1.1182424^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :1.155362 |
| When c Myc increases , ARF binds with c Myc and dramatically blocks c Myc ' s ability to activate transcription and induce hyperproliferation and transformation . 1.155362^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Myc and E2F1 induce p 53 through p14ARF independent mechanisms in human fibroblasts . p19ARF is induced in response to oncogene activation or during cellular senescence in mouse embryo fibroblasts , triggering p 53 dependent and p 53 independent cell cycle arrest and apoptosis . ^^^ We have studied the involvement of human p14ARF as a regulator of p 53 activity in normal human skin fibroblasts ( NHFs ) or WI 38 lung embryonic fibroblasts expressing conditional Myc or E2F1 estrogen receptor fusion proteins . ^^^ In contrast , Myc activation did not induce any significant increase in p14ARF mRNA or protein levels in neither NHFs nor WI 38 fibroblasts within 48 h . ^^^ Myc and E2F1 induced p 53 and cell cycle arrest even after silencing of p14ARF using short interfering RNA . ^^^ Our results indicate that p 53 phosphorylation , but not p14ARF , plays a major role for the induction of p 53 in response to Myc and E2F1 activation in normal human fibroblasts . . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Furthermore , p 53 , p14ARF , c myc and E2F1 , but not E1A , induced p53S15 phosphorylation was substantially reduced in AT fibroblasts ( GM 05823 ) . ^^^ Functionally , ectopic expression of p14ARF and c myc inhibited the proliferation of IMR 90 but not ATM null GM 05823 cells , and p14ARF induced inhibition of MCF 7 cell proliferation was significantly attenuated by downregulation of ATM by RNAi . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Expression of the p14ARF tumour suppressor is induced by hyperproliferative signals produced by RAS , MYC and other oncogenes . p14ARF quenches inappropriate mitogenic signaling by activating the p 53 pathway , and the frequent loss of p14ARF in human cancer diminishes the duration and level of the p 53 response . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| The alternative reading frame product ( p19ARF ) of the mouse INK4a / ARF locus is induced by oncoproteins such as Myc and E1A as part of a checkpoint response that limits cell cycle progression in response to hyperproliferative signals . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Among recent findings are connections to the CD95 / Fas and TNF pathways and roles for the tumor suppressor p19ARF and the c Myc interacting adaptor protein Binl in mediating cell death . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Others have shown that part of Myc ' s ability to induce apoptosis depends on induction of p19arf . ^^^ Furthermore , Bmi 1 collaborates with Myc in enhancing proliferation and transformation of primary embryo fibroblasts ( MEFs ) in an ink4a ARF dependent manner , by prohibiting Myc mediated induction of p19arf and apoptosis . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| While MYC is the well characterized CTCF target , the inhibitory effects of CTCF on cell growth could not be ascribed solely to repression of MYC , suggesting that additional CTS driven genes involved in growth regulatory circuits , such as p19ARF , are likely to contribute to CTCF induced growth arrest . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Oncogene cooperation by Tbx 3 correlates with an ability of Tbx 3 to suppress the induction of p19ARF and p 53 that is typically caused by overexpression Myc and Ras , and to protect against Myc induced apoptosis . ^^^ Whereas Tbx 3 is capable of interfering with apoptosis caused by excessive Myc levels , a Tbx 3 mutant lacking its C terminal repression domain shows no anti apoptotic activity and fails to repress levels of p19ARF or p 53 . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Acute MYC expression increases p 53 or ARF levels and induces apoptosis , and previous transgenic animal studies revealed frequent inactivating mutations of p 53 or p19ARF in transgenic Myc induced lymphomas . ^^^ In contrast , the MYC point mutants failed to induce Bim , promoting murine lymphomas that escaped both wild type p 53 and p19ARF , and in doing so , evaded apoptosis . . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Specifically , we were interested in the expression of the tumor suppressor gene Cdkn2b ( p 15 ( INK4b ) ) in MML because this gene is expressed during myeloid differentiation and its inactivation by methylation has been shown to be important for the development of human acute myeloid leukemia . mRNA levels for p 15 ( INK4b ) and another INK 4 gene p 16 ( INK4a ) were examined in monocytic Myb tumors and were compared with expression of the same genes in c myc transformed monocytic tumors that do not express c Myb . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| In the present study , we examined murine monocyte / macrophage tumors with deregulated c myc for evidence of Ink 4 gene inactivation . p 15 ( Ink4b ) mRNA and protein were detected in the majority of leukemias , and p 16 ( Ink4a ) mRNA and protein were highly expressed in two of them . pRb was in a hypophosphorylated state in most of the neoplasms indicating that the Cdk inhibitors that were expressed in the cells were functional . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| The expression of c myc , MDM 2 , c erbB 2 , EGFR , p 53 , p 14 ( ARF ) , p 16 ( INK 4 ) , p 21 ( WAF 1 ) and nm 23 was detected by immunohistochemical assay . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| These include rapid induction of cyclin dependent kinase inhibitors , such as those in the Cip / Kip and Ink 4 families and down regulation of c myc mRNA and c Myc transcriptional activity . ^^^ This was discovered using a cell line which constitutively expresses c myc from a retrovirus vector and which was reported to have undergone deletion of genes encoding the Ink 4 tumor suppressors p 15 and p 16 . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| To identify the possible genes included in the abnormal chromosome regions , selected cases were analyzed for P 53 , P 16 ( INK4a ) , RB , C MYC , N MYC , BCL 2 , BCL 6 , CDK 4 , and BMI 1 gene alterations . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| To better understand these mechanisms in long term cultured lymphocytes we have characterized two human long term cultured IL 2 dependent T cell lines regarding telomere length , telomerase activity , and the expression of selected cell cycle regulators ( pRb , p 53 , cyclin E , cyclin D 1 , cyclin D 2 , cyclin D 3 , cdk 4 , p 16 ( INK4a ) , p 21 ( WAF 1 ) , p 27 ( KIP 1 ) , c myc , bcl 2 , and NPAT ) . ^^^ The growth inhibitory activity of p 16 ( INK4a ) seemed to be abrogated by enhanced expression of cyclin D 2 , cdk 4 , and c myc in one T cell line and overexpression of cyclin E in the second T cell line . . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| These cells have normal Ki ras , p 53 , c myc , and p 16 ( INK4A ) genotypes . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| The gastrointestinal carcinogenesis is suggested to be associated with the decrease of total genomic DNA methylation ; hypomethylation of certain specific oncogenes such as c myc , c Ha ras , c fos and alpha fetoprotein ; and hypermethylation of the promoter of some tumor suppressor genes containing p 16 ( INK4A ) , E cadherin and hMLH 1 genes . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| In nodules and / or HCCs of Wistar and BN rats , low or no increases in c myc , Cyclins D 1 , E , and A , and E2F1 expression , and Cyclin CDKs complex formation were associated with p 16 ( INK4A ) overexpression and pRb hypophosphorylation . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| The expressions of p 16 ( INK4A ) , p 21 ( WAF 1 ) , APC and c myc genes were observed by using RT PCR . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| To assess the cellular mechanisms underlying the mesangial cell proliferation and glomerulosclerosis in progressive human IgA nephropathy ( IgAN ) , we examined the expression of E2F1 , Rb , c Myc , proliferating cell nuclear antigen ( PCNA ) , cyclins ( D 1 , E and A ) , cyclin dependent kinase 2 ( CDK 2 ) and CDK inhibitors ( p 21 ( waf 1 ) , p 27 ( kip 1 ) , 57 ( kip 2 ) and p 16 ( ink4a ) ) by immunohistochemistry in renal biopsy specimens . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Transcription levels of Dnmt 1 , mbd 2 , MeCP 2 , p 16 ( INK4A ) , hMSH 2 and c myc were detected by using real time PCR or RT PCR . ^^^ Promoter methylation of p 16 ( INK4A ) , c myc and hMSH 2 genes was assayed by methylation specific PCR ( MSP ) and sequencing ( mapping ) . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| While c Kit ( hi ) IL 7Ralpha progenitors are absent , c Kit ( lo ) IL 7Ralpha+ progenitors are abundant in the lymph nodes ( LNs ) . c Kit ( lo ) IL 7Ralpha+ progenitors undergo abortive T cell commitment in the LNs and become arrested in the G 1 phase of the cell cycle because they fail both to up regulate c myb , c myc , and cyclin D 2 and to repress junB , p 16 ( INK4a ) , and p 21 ( Cip1 / WAF ) . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Thus , p 16 ( INK4A ) , although unable to repress the expression of deregulated cyclin E and c Myc , functionally inactivated these potential oncogenes . p 16 ( INK4A ) arrested cells showed morphologic changes , induction of T cell specific surface markers and repression of telomerase activity , suggesting differentiation . ^^^ Taken together , p 16 ( INK4A ) reconstitution in p 16 ( INK4A ) deficient T ALL cells induced cell cycle arrest in the presence of cyclin E and c Myc expression , uncoupled growth from cell cycle progression and caused a sequential process of growth , differentiation and apoptosis . . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Coexistence of copy number changes of different genes ( INK4A , erbB 1 , erbB 2 , CMYC , CCND 1 and ZNF 217 ) in urothelial tumors . ^^^ The aim of this study was to establish the frequency of combinatorial and separate copy number changes of INK4A ( 9p21 ) , erbB 1 ( 7p11 ) , erbB 2 ( 17q17 21 ) , CMYC ( 8q24 ) , CCND 1 ( 11q13 ) and ZNF 217 ( 20q13 ) in urothelial tumors ; a tissue microarray of 159 urothelial bladder tumors was analyzed by fluorescence in situ hybridization . ^^^ The most frequent genetic change was deletion of INK4A ( 60 % of aberrant tumors ) , followed by increased copy number changes of ZNF 217 ( 36 % ) , CCND 1 ( 28 % ) , CMYC ( 12 % ) and erbB 1 ( 4 % ) . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| In this system , we could associate a down regulation of the INK4A locus with anchorage independent growth and with resistance to Ras induced senescence and link p 53 mutations and c myc overexpression with tumorigenicity . . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Reduced c Myc signaling triggers telomere independent senescence by regulating Bmi 1 and p 16 ( INK4a ) . ^^^ Normal human fibroblasts with one copy of the c myc gene inactivated by targeted homologous recombination switched with an increased frequency to a telomere independent senescent state mediated by the cyclin dependent kinase inhibitor p 16 ( INK4a ) . p 16 ( INK4a ) expression was regulated by the Polycomb group repressor Bmi 1 , which we show is a direct transcriptional target of c Myc . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| The addition of the c myc epitope at the C terminus of Arf 1 resulted in a mutant ( arf 1 myc arf 2 ) that supported vegetative growth and rescued cells from supersensitivity to fluoride , but homozygous diploids failed to sporulate . arf 1 myc arf 2 mutants completed both meiotic divisions but were unable to form spores . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Myc signaling via the ARF tumor suppressor regulates p 53 dependent apoptosis and immortalization . ^^^ Establishment of primary mouse embryo fibroblasts ( MEFs ) as continuously growing cell lines is normally accompanied by loss of the p 53 or p 19 ( ARF ) tumor suppressors , which act in a common biochemical pathway . myc rapidly activates ARF and p 53 gene expression in primary MEFs and triggers replicative crisis by inducing apoptosis . ^^^ MEFs that survive myc overexpression sustain p 53 mutation or ARF loss during the process of establishment and become immortal . ^^^ MEFs lacking ARF or p 53 exhibit an attenuated apoptotic response to myc ab initio and rapidly give rise to cell lines that proliferate in chemically defined medium lacking serum . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Unlike genes such as Myc , adenovirus E1A , and E2F 1 , which , when overexpressed , activate the ARF p 53 pathway and trigger apoptosis , DMP 1 , like ARF itself , does not induce programmed cell death . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| In cultured primary mouse embryo fibroblasts , c Myc activates the p 19 ( ARF ) Mdm 2 p53 tumor suppressor pathway , enhancing p 53 dependent apoptosis but ultimately selecting for surviving immortalized cells that have sustained either p 53 mutation or biallelic ARF deletion . ^^^ Disruption of the ARF Mdm 2 p53 tumor suppressor pathway in Myc induced lymphomagenesis . ^^^ Here we report that p 53 and ARF also potentiate Myc induced apoptosis in primary pre B cell cultures , and that spontaneous inactivation of the ARF Mdm 2 p53 pathway occurs frequently in tumors arising in Emu myc transgenic mice . ^^^ Many Emu myc lymphomas sustained either p 53 ( 28 % ) or ARF ( 24 % ) loss of function , whereas Mdm 2 levels were elevated in others . ^^^ Emu myc transgenic mice hemizygous for ARF displayed accelerated disease ( 11 week mean survival ) , and 80 % of these tumors lost the wild type ARF allele . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Arf and Mdm 2 co localize in the nucleolus in response to activation of the oncoprotein Myc and as mouse fibroblasts undergo replicative senescence . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| ARF is induced by activated oncogenes sucll as c myc , E1A and E2F 1 . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| METHOD : The expression of genes that promote ( c myc , Bax , BclxS ) or protect ( Bcl 2 , BclxL ) from cell death was studied by Northern blot , Western blot , and immunohistochemistry in murine kidneys following ARF induced by folic acid or in renal tubular epithelial cells ( MCT ) stressed in culture . ^^^ RESULTS : Renal mRNA levels encoding for c myc and BclxL were elevated in ARF while the Bcl2 / Bax ratio was decreased ( Bcl 2 decreased and Bax increased ; P < 0 . 05 ) . ^^^ These deficits predispose to cell death induced by persistent lethal factors such as TNF alpha that is increased in ARF and a potential source of increased c myc , a downstream facilitator of cell death . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| TBX 2 represses the Cdkn2a ( p 19 ( ARF ) ) promoter and attenuates E2F1 , Myc or HRAS mediated induction of Cdkn2a ( p 19 ( ARF ) ) . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Myc activation leads to a selection for inactivation of ARF or p 53 , allowing cell survival and tumor progression . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Paradoxically , Myc overexpression also triggers the ARF p 53 apoptotic program , which is activated when MEFs undergo replicative crises following culture ex vivo . ^^^ The rare immortal variants that arise from these cultures generally suffer mutations in p 53 or delete Ink4a / ARF , and Myc greatly increases the frequency of these events . ^^^ Thus , the regulation of TERT and telomerase activity is complex and is also regulated by factors other than Myc , ARF , or p53 . . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| The ARF and p 53 tumor suppressors mediate Myc induced apoptosis and suppress lymphoma development in E mu myc transgenic mice . ^^^ Eighty percent of lymphomas arising in wild type E mu myc transgenics have alterations in the ARF Mdm 2 p53 tumor suppressor pathway characterized by deletions in ARF , mutations or deletions of p 53 , and overexpression of Mdm 2 . ^^^ The absence of Bax did not alter the frequency of biallelic deletion of ARF in lymphomas arising in E mu myc transgenic mice or the rate of tumorigenesis in ARF null mice . ^^^ Thus , the loss of Bax eliminates the selection of p 53 mutations and deletions , but not ARF deletions or Mdm 2 overexpression , during Myc induced tumorigenesis , formally demonstrating that Myc induced apoptotic signals through ARF / Mdm2 and p 53 must bifurcate : p 53 signals through Bax , whereas this is not necessarily the case for ARF and Mdm2 . . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| E2F 1 up regulates c Myc and p 14 ( ARF ) and induces apoptosis in colon cancer cells . ^^^ Of mechanistic importance , overexpression of E2F 1 caused a G ( 2 ) / M arrest followed by increased levels of c Myc and p 14 ( ARF ) proteins . ^^^ Overexpression of E2F 1 triggers apoptosis and is associated with up regulation of c Myc and p 14 ( ARF ) proteins and down regulation of Mcl 1 . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| ARF differentially modulates apoptosis induced by E2F1 and Myc . ^^^ In contrast , the ability of Myc to induce apoptosis is diminished in the absence of ARF . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| However , even tumours arising in E ( mu ) myc / Arf null animals are thought to be clonal . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Here we have analysed survival of inducible c Myc overexpressing cell lines derived from U2OS human osteosarcoma cells , which carry wild type pRb and p 53 and are deficient for p 16 and ARF expression . ^^^ Induced U2OS Myc cells neither underwent apoptosis spontaneously nor upon reconstitution of the ARF p 53 axis and / or serum starvation . ^^^ Similar apoptotic effect was observed upon down modulation of endogenous E2Fs through overexpression of E2F binding site oligonucleotides in U2OS Myc cells , upon expression of RbDeltacdk or dnDP 1 in the Myc amplified HL 60 ( ARF ; p 53 ) human leukemia cells , and upon co transfection of Myc and RbDeltacdk in SAOS 2 ( ARF+ ; p 53 ) human osteosarcoma cells but not in human primary fibroblasts . ^^^ Our data indicate that in contrast to normal cells , Myc overexpressing human cancer cells need E2F activity for their survival , regardless of their ARF and p 53 status , a notion that may have important implications for antineoplastic treatment strategies . . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Conditional expression of CTCF in WEHI 231 mimicked BCR ligation with activated cells showing repressed expression of MYC , enhanced expression of p 27 , p 21 , p 53 , and p 19 ( ARF ) , and inhibition of cell growth and induction of apoptosis . ^^^ In keeping with a central role for CTCF in control of B cell death , conditional expression of a CTCF antisense construct in WEHI 231 resulted in inhibition of p 27 , p 21 , p 53 , and p 19 ( ARF ) in association with enhanced expression of MYC . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Mice expressing an Emu Myc transgene in B lymphocytes develop lymphomas , the majority of which sustain mutations of either the Arf or p 53 tumor suppressors . ^^^ In contrast , Myc induced apoptosis and the frequency of Arf and p 53 mutations in lymphomas were unaffected by E2f1 loss . ^^^ Therefore , Myc does not require E2f1 to induce Arf , p 53 , or apoptosis in B cells , but depends upon E2f1 to accelerate cell cycle progression and downregulate p 27 ( Kip 1 ) . . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Importantly , detailed examination of one of the WI 38 / hTERT cultures during the accelerated growth phase revealed overexpression of the c myc and Bmi 1 oncogenes , as well as loss of p 14 ( ARF ) expression . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| However , activated myc can initiate ARF dependent activation of p 53 and apoptosis as well . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Antagonism of Myc functions by Arf . ^^^ The Arf Mdm 2 p53 tumor suppressor pathway is activated by sustained hyperproliferative signals emanating from oncoproteins such as Myc . ^^^ A recent study reveals a novel level of feedback control , whereby induced p 19 ( Arf ) binds to Myc and blocks cell proliferation by selectively impairing its transactivation functions . . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Deregulated expression of c Myc induces ARF expression and apoptosis through the ARF Mdm 2 p53 axis . ^^^ Our recent study reveals a new direct role for ARF in controlling c Myc ' s oncogenic activity that is independent of p 53 . ^^^ ARF binds to and selectively impairs the transactivation ability of c Myc while leaving its transrepression ability intact . ^^^ Biologically , ARF prevents hyper proliferation and transformation caused by c Myc and enhances c Myc induced apoptosis independently of p 53 . ^^^ The ARF tumor suppressor : keeping Myc on a leash . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Twelve ( 46 % ) of 26 lymphoblastic B cell lymphomas exhibited changes in the p 19 ( Arf ) Mdm 2 p53 tumor suppressor axis , an important pathway for Myc dependent apoptosis . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| We have previously demonstrated that c Myc impairs p 53 mediated apoptosis in K 562 human leukemia cells , which lack ARF . ^^^ Our data suggest that elevated levels of Myc counteract p 53 activity in human tumor cells that lack ARF . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Strikingly , tumors ultimately arising in E mu Myc ; Odc ( + / ) transgenics lacked deletions of Arf , suggesting that targeting Odc forces other routes of transformation . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| We show that tumor suppressor ARF and ATM / ATR kinase pathways cooperate in the induction of apoptosis in response to elevated expression of c myc , beta catenin or human papilloma virus E 7 oncogenes . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| This is reminiscent of the c Myc > p 19 ( ARF ) mid R : Mdm 2 pathway and might function as a complementary arm to ensure the proper cellular response to oncogenic and / or apoptotic stimuli . . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Bcl xL gain of function and p 19 ARF loss of function cooperate oncogenically with Myc in vivo by distinct mechanisms . ^^^ Overexpression of Bcl xL , loss of p 19 ARF , and loss of p 53 all accelerate Myc oncogenesis . ^^^ While Bcl xL blocks Myc induced apoptosis , inactivation of p 19 ARF enhances it . ^^^ Bcl xL and p 19 ARF loss together synergize to further accelerate Myc oncogenesis . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Interestingly , p 53 and c Myc are functionally connected by some of these E 3 enzymes and their regulator ARF , although these proteins play opposite roles in controlling cell growth and proliferation . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| The development of a lung cancer requires multiple genetic changes , consisting of the activation of oncogenes , including the K ras and myc genes , and of inactivation of tumour suppressor genes , including the Rb , p 53 and CDKN 2 genes . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Therefore , we analysed methylation of the VHL , CDKN 2 , MYC , and H 19 genes in primary RCC samples . ^^^ None of the 11 RCCs methylated at VHL had evidence of methylation at either CDKN 2 or MYC ( methylation at CDKN 2 was , however , detected in 3 % , or 1 / 33 , of RCCs without VHL methylation ) . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Additionally , the expression of SRC , c myc and p16 / CDKN 2 were studied . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| In the glioblastomas with no alterations of CDKN2A , CDK 4 or RB 1 , several other genes ( CCND 1 , CCND 2 , CCND 3 , CDK 6 , E2F , CDK 7 , MYC and MYCN ) whose products take part in cell cycle regulation were examined . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Twenty primary central nervous system lymphomas ( PCNSL ) from immunocompetent patients ( nineteen B cell lymphomas and one T cell lymphoma ) were investigated for genetic alterations and / or expression of the genes BCL 2 , CCND 1 , CDK 4 , CDKN1A , CDKN2A , MDM 2 , MYC , RB 1 , REL , and TP 53 . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| FISH analysis of BK 10 using chromosome arm specific paints , centromere probes , and oncogene / tumor suppressor gene specific probes revealed a deletion of CDKN2A ( p 16 ) in all copies of chromosome 9 , a low level amplification of MYC ( five copies ) , and loss of one copy of TP 53 ; detected the presence of the Y chromosome in a hidden translocation ; and detected four copies of ERBB 2 . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| To date , molecular genetic studies of CML BC have mainly focused on alterations of well known tumor suppressor genes ( e . g . , TP 53 , CDKN2A , and RB 1 ) and oncogenes ( e . g . , RAS and MYC ) , whereas limited knowledge is available about the molecular genetic correlates of the unbalanced chromosomal abnormalities . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| The gene ratios c MYC : cyclin dependent kinase ( CDK ) N2A and CCND 1 : CDKN2A correlate with poor prognosis in squamous cell carcinoma of the head and neck . ^^^ EXPERIMENTAL DESIGN : Extracted DNA from diagnostic biopsies of 78 untreated patients were analyzed by real time PCR with specific primers for c MYC , CCND 1 , and CDKN2A . ^^^ Gene copy number ratios were calculated by dividing the copy number of c MYC or CCND 1 with CDKN2A . ^^^ RESULTS : Enhanced gene ratio of c MYC : CDKN2A was detected in 35 of 78 ( 45 % ) and enhanced ratio of CCND 1 : CDKN2A in 36 of 78 ( 46 % ) of the cases . ^^^ The c MYC : CDKN2A and CCND 1 : CDKN2A ratios correlated with disease specific survival with respect to death ( P = 0 . 042 and 0 . 049 , respectively ; Log rank test ) . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| The most commonly identified genetic alterations associated with the FCL transformation are TP 53 gene mutations , inactivation of CDKN2A and CDKN2B genes and deregulation of the C MYC gene . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| The telomerase expressing cells show no features of transformation in vitro and have stable genomes with diploid karyotypes , do not express exceptionally high levels of c myc and have wild type , unmethylated CDKN2A genes . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| In fact , several tumor suppressors and oncogenes have been shown to be involved in melanoma pathogenesis , including CDKN2A , PTEN , TP 53 , RAS and MYC , though they have not been related to melanoma subtypes or validated as prognostic markers . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Moreover , several tumour suppressors and oncogenes have been shown to be involved in melanoma pathogenesis , including CDKN2A , PTEN , TP 53 , RAS and MYC , but have not been related to melanoma subtypes or validated as prognostic markers . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Finally , small regions of deletion and amplification , often including genes known to be involved in leukemia progression ( for example MYC , TP 53 , CDKN2A , and KIT ) , were identified . . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| The authors summarize findings on apoptosis programmed cellular death , incl . basic data on expression of genes promoting ( p 53 , c myc , MTS 1 and fas ) or inhibiting ( bcl 2 , bcr abl ) this process . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Also in bladder carcinoma the study of cellular differentiation markers has been replaced by that of genotypic alterations , and , mainly with the help of immunohistochemistry , of the expression of genes involved in cell proliferation and death , such as MTS 1 , TP 53 , Rb , c myc , Bcl 2 , c erb B 2 . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Fourteen cases of DCIS and 11 of DCIS with minimal invasion were analysed for mRNA levels of beta actin , EGFR , c cerbB 2 , MTS 1 , k ras , RB , BRCA 1 , cyclin E , and c myc genes . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Conventional RT PCR revealed that E cadherin transfection suppressed expression of mts 1 mRNA and increased that of c myc and MT 1 MMP . ^^^ In quantitative RT PCR analysis , levels of c myc and MT 1 MMP mRNA were elevated by to 2 . 56 and 2 . 22 fold , respectively , in the E cadherin transfectant , whereas mts 1 was 7 . 14 fold suppressed compared to parental cells . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Expression of p16INK4 suppressed cellular transformation of primary rat embryo fibroblasts by oncogenic Ha Ras and Myc , but not by Ha Ras and E1a . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Immortalization of HEN by HPV 16 resulted in enhanced expression of H ras , c myc , B myb , p 53 , p16INK4 and PCNA mRNA ; enhanced expression of p 16 and PCNA proteins ; decreased expression of WAF1 / p21 / Cip1 / Sid1 and fibronectin mRNA ; and decreased p 53 protein . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| To investigate the regulatory mechanism of the expression of the multidrug resistance gene ( mdr 1 ) and the multidrug resistance associated protein gene ( mrp ) , we investigated if p 53 , WT 1 , RB , C myc , N myc , cyclin D 1 , p16INK4 ( p 16 ) are involved in the acquirement of multidrug resistance phenotype ( MDR ) in human vincristine ( VCR ) resistant cells of leukemia / lymphoma cell lines . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| These include myc proto oncogene , 40S ribosomal protein S 19 , heat shock proteins , leukosialin S ( CD 43 ) , integrin alphaL ( CD11A ) , calgranulin ( A ) , and CDK 4 inhibitor ( p16ink4 ) . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| In conclusion , our study shows that p16INK4 , c myc and p 53 alterations occur in 15 % , 25 % and 13 % of PMBLs , respectively . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Mutual requirement of CDK 4 and Myc in malignant transformation : evidence for cyclin D1 / CDK4 and p16INK4A as upstream regulators of Myc . ^^^ Moreover , we find that p16INK4a and the Rb related protein p 107 which releases Myc after phosphorylation by cyclin D1 / CDK4 efficiently block Myc ' s activity as a transcriptional transactivator and as an oncogene . ^^^ We conclude that both p16INK4a and cyclin D / CDK4 complexes are upstream regulators of Myc and directly govern Myc function in transcriptional transactivation and transformation via the pocket protein p107 . . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Cyclin E and c Myc promote cell proliferation in the presence of p16INK4a and of hypophosphorylated retinoblastoma family proteins . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Constitutive expression of either Myc or cyclin E can prevent growth arrest by p16INK4a ( an inhibitor of cyclin D / CDK4 , but not of cyclin E / CDK2 ) . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| RESULTS : Molecular mechanisms altered in lung cancer include induced expression of oncogenes , such as RAS , MYC , c erbB 2 , and BCL 2 , and loss of tumor suppressor genes , such as RB , p 53 , and p16INK4A . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| OBJECTIVE : To study the effect of compound Chinese drug Bailong on the transcription of Cyclin Dependent Kinase Inhibitor ( CKI ) p16INK4a , p 21 and Rb , c myc genes , and the relationship between gene expression and cAMP PKA pathway . ^^^ Being same as p16INK4a , tumor suppressor genes Rb , p 21 and oncogene c myc expression were all affected by Bailong . ^^^ CONCLUSION : Bailong can affect many anticancer genes ( including p16INK4a , p 21 and Rb genes ) and oncogenes ( including c myc ) transcription by regulating cAMP PKA pathway . . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| PURPOSE : Several genes are reported to be implicated in bladder carcinogenesis , including p 53 , p16INK4a , pRb , erbB 2 , Cyclin D 1 , H ras , EGFR , and c myc . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| To determine how altered expression of these gene products contribute to HNSCC progression , we examined expression of epidermal growth factor receptor ( EGFR ) , cyclins , p16INK4A , c myc , proliferating cell nuclear antigen ( PCNA ) , and telomerase in archival pathology specimens by immunohistochemistry . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| We find that human diploid fibroblasts ( HDFs ) that are specifically deficient for p16INK4a achieve anchorage independence when transduced with retroviruses encoding telomerase ( hTERT ) and either Ras or Myc . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| The expressions of p16INK4A , p21WAF1 , p 53 , p 73 , c Ha ras and c myc genes mRNA were detected by using reverse transcription PCR ( RT PCR ) . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| By starting with strains of primary fibroblast ( Leiden and Q 34 cells ) that are genetically deficient for p16INK4a , we have been able to generate anchorage independent colonies simply by addition of telomerase ( hTERT ) and either Ras or Myc . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Multiple genetic defects , such as mutations of the p 53 tumor suppressor gene , p16INK4A , and p 21 , loss of p 27 expression , deletion of retinoblastoma , increased copy number of C MYC , and decreased expression of the A MYB gene , have been described . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| However , HPrECs expressing c Myc lack a Rb / p16INK4a checkpoint and can be transformed without the need for additional genetic lesions in that pathway . ^^^ Myc stabilizes telomere length in HPrEC through up regulation of hTERT expression and overrides the accumulation of cell cycle inhibitory proteins , such as p16INK4a . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| Current markers with potential prognostic value include p 53 , Bcl 2 , p16INK4A , p27Kip1 , c Myc , AR , E cadherin and vascular endothelial growth factor . ^^^ |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and P01106 |
Pubmed |
SVM Score :0.0 |
| NA |
|