| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.51258321 |
| The antagonism between RB and c Abl / p73 may modulate the function of p 53 to direct the choice between growth arrest and apoptosis in DNA damaged cells . . 0.51258321^^^ |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| The fidelity of this mimicry by okadaic acid extends to the phosphorylation of the 27 hsp complex , stathmin , eIF 4E , myosin light chain , nucleolin , epidermal growth factor receptor , and other cdc 2 kinase substrates ( c abl , RB , and p 53 ) . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| One target of RB is a proto oncoprotein , the c Abl tyrosine kinase . ^^^ RB binds to the ATP binding lobe in the kinase domain and inhibits the nuclear pool of c Abl in quiescent and G 1 cells . ^^^ Phosphorylation of RB at G1 / S releases c Abl , leading to the activation of this nuclear tyrosine kinase . ^^^ Interestingly , wild type c Abl , in both its kinase active and inactive forms , can also overcome RB . ^^^ Thus , the growth stimulating function of the kinase defective c Abl is dependent on the binding and the abrogation of RB function . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| We used fibroblasts containing disruptions of the Rb or p 53 genes to genetically test the role of these proteins in c Abl growth suppression . ^^^ We find that c Abl requires p 53 but not Rb to suppress growth . c Abl binds p 53 in vitro and enhances p 53 dependent transcription from a promoter containing p 53 DNA binding sites . ^^^ |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| We can further speculate that the loss of p 53 function , at the time of blastic crisis of CML , may play a role , in combination with other genetic changes ( p 210 BCR / ABL , Rb gene abnormality , others to be defined ) , in inducing disturbances in cell proliferation , differentiation , and apoptosis . . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| RB contains at least two protein binding pockets : the large A / B pocket , which interacts with E2F and the D type cyclins , and the C pocket , which interacts with the nuclear c Abl tyrosine kinase . ^^^ A complex containing E2F , RB , and c Abl is detected in vivo and can be assembled in vitro . ^^^ SE delta does compete with RB for binding to c Abl and is fully capable of inhibiting the c Abl tyrosine kinase . ^^^ Thus , SE delta can inactivate RB while maintaining the inhibition of E2F and c Abl . ^^^ |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| Here we show that the tyrosine kinase activity of nuclear c Abl is regulated in the cell cycle through a specific interaction with the retinoblastoma protein ( RB ) . ^^^ A domain in the C terminus of RB , outside of the A / B pocket , binds to the ATP binding lobe of the c Abl tyrosine kinase , resulting in kinase inhibition . ^^^ The RB c Abl interaction is not affected by the viral oncoproteins that bind to RB . ^^^ Hyperphosphorylation of RB correlates with release of c Abl and activation of the tyrosine kinase in S phase cells . ^^^ The nuclear c Abl tyrosine kinase can enhance transcription , and this activity is inhibited by RB . ^^^ |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| Role of c abl oncogene in chronic myeloid leukemia ( CML ) , bcl 2 , in lymphomas , N myc in neuroblastomas and retinoblastoma ( Rb ) gene in retinoblastomas is well understood and used in designing proper therapeutic approaches . ^^^ |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| In the absence of TGF beta 1 , transient expression of RB in 5 Abl expressing cells resulted in decreased c myc transcription , inhibition of GAL 4 E2F 1 driven transactivation and inhibition of cellular proliferation . ^^^ RB and 5 Abl were found to physically associate in vivo and in vitro via 5 Abl ' s ATP binding region . ^^^ In summary , these studies established that in myeloid cells : ( 1 ) 5 Abl binds RB resulting in increased E2F 1 driven c myc transcription , and ( 2 ) an alternative pathway exists for TGF beta 1 mediated growth inhibition of 5 Abl transformed cells , in which increased rather than decreased E2F mediated c myc transcription is observed . . ^^^ |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| RB contains at least three distinct protein binding functions : ( 1 ) the A / B pocket , which binds proteins with the LXCXE motif ; ( 2 ) the C pocket , which binds the c Abl tyrosine kinase ; and ( 3 ) the large A / B pocket , which binds the E2F family of transcription factors . ^^^ These RB mutants can bind LXCXE proteins , c Abl , and E2F even after they become phosphorylated at the remaining nonmutated sites . ^^^ |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| At least three distinct protein binding activities have been identified in RB : the large A / B pocket binds E2F , the A / B pocket binds the LXCXE peptide motif , and the C pocket binds the nuclear c Abl tyrosine kinase . ^^^ |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| Cytotoxicity is overcome by coexpression of the apoptosis antagonist E1B 19K protein , and partially overcome by full length retinoblastoma protein ( Rb ) or the C pocket fragment of Rb ( SEA ) that associates with c Abl . c Abl is also highly toxic to Saos 2 cells that are deficient for both Rb and p 53 , indicating that cell death is not the result of inhibition through c Abl of the anti apoptotic function of Rb . ^^^ Unlike c Abl mediated cell death , apoptosis by p 53 is antagonized efficiently only by full length Rb with intact A / B pocket but not by SEA . ^^^ Thus , c Abl with intact kinase and PolII / actin binding domains can affect tumor cell survival independently of Rb and p53 . . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| The cytostatic function of c Abl is controlled by multiple nuclear localization signals and requires the p 53 and Rb tumor suppressor gene products . c Abl is a non receptor protein tyrosine kinase lacking a clear physiological role . ^^^ Further , we demonstrate that the Abl cytostatic effect requires both the Rb and p 53 tumor suppressor gene products . ^^^ These results indicate that Abl inhibits cell proliferation by interacting with central elements of the cell cycle control apparatus in the nucleus , and suggest a direct connection between p 53 and Rb in this growth inhibitory pathway . . ^^^ |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| Cells arrested in G 1 by the 5 Abl tyrosine kinase do not express cyclin A despite the hyperphosphorylation of RB . ^^^ As a result , 5 Abl does not block the hyperphosphorylation and inactivation of the retinoblastoma protein RB . ^^^ |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| The presence of the Rb c box peptide in the cytoplasm inhibits p210bcr abl transforming function . ^^^ In order to test if the carboxyl terminal polypeptide of the Retinoblastoma ( Rb ) tumor suppressor protein , could be used to suppress the growth factor independent growth phenotype of p210bcr abl positive myeloid cells , we introduced a truncated form of the 3 ' end of the Rb cDNA encoding its last 173 amino acid residues ( Rb C box ) which localize into the cytoplasm where the p210bcr abl transforming protein is found , into myeloid cells ( 32D ) which depends on the p210bcr abl protein for IL 3 growth factor independent growth ( 32D p 210 ) . ^^^ The expression of the plasmid vectors carrying the Rb C box cDNAs was shown to inhibit the abl tyrosine specific protein kinase activity of the p 210 ( bcr abl ) oncoprotein and to suppress the IL 3 independent growth phenotype of the 32D p 210 cells . ^^^ These results suggest that the cytoplasmic localization of the p 210 ( bcr abl ) allows it to escape the effect of intranuclear proteins such as Rb which negatively regulate the p 145 ( c abl ) kinase . . ^^^ |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| Functionally , the association of p21 / cyclin A / cdk2 decreased histone H 1 phosphorylation in vitro , as observed in immunoprecipitations followed by kinase assays , and affected other substrates , such as the C terminus of Rb protein involved in c Abl and histone deacetylase 1 ( HDAC 1 ) regulation . ^^^ |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| Functionally , the association of p21 / cyclin A / cdk2 decreased the histone H 1 phosphorylation in vitro , as observed in immunoprecipitations followed by kinase assays , as well as affecting other substrates such as the C terminus of Rb protein involved in c Abl and HDAC 1 regulation . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| In the nucleus , c Abl activity is negatively regulated by the retinoblastoma protein ( RB ) and positively regulated by DNA damage signals . ^^^ The inhibition of c Abl by RB is consistent with RB ' s ability to block apoptosis ; while the activation of c Abl by ATM is consistent with ATM ' s ability to activate cell death . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| In DU 145 cells , RB mediated apoptosis involved biphasic activation of ABL kinase . ^^^ ABL kinase was activated within minutes of irradiation , but in the presence of RB expression ABL kinase activation was enhanced 48 h after irradiation , coincident with the onset of cell death . ^^^ Apoptosis was inhibited by RB mutants with constitutive ABL binding , but ABL overexpression overcame the effect of the RB mutant constructs . ^^^ Expression of kinase dead ABL had a dominant negative effect on RB mediated cell death . ^^^ The data show that after gamma irradiation , intact RB mediates transcriptional activation that leads to activation of JNK and late activation of ABL kinase . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| ErPC 3 exerts at least part of its antineoplastic activity by apoptosis , and this chain of events comprises early changes in the lipid raft fraction of the cellular membrane as well as modulation of different signal molecules , such as Abl , Bcr Abl ( fusion protein ) , and Rb . . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| Tumor necrosis factor alpha induced apoptosis requires p 73 and c ABL activation downstream of RB degradation . ^^^ We show here the identification of two apoptotic effectors , i . e . , c ABL tyrosine kinase and p 73 , which are activated by TNF alpha following RB degradation . ^^^ In cells expressing a degradation resistant RB protein ( RB MI ) , TNF alpha does not activate c ABL . ^^^ Thymocytes isolated from Rb ( MI / MI ) , Abl ( / ) , or p 73 ( / ) mice are resistant to TNF alpha induced apoptosis compared to their wild type counterparts . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| Loss of c abl facilitates anchorage independent growth of p 53 and RB deficient primary mouse embryonic fibroblasts . ^^^ Here , we report that the loss of c abl facilitates transformation . c abl knockout mouse embryonic fibroblasts ( MEFs ) immortalized by SV 40 T antigen acquired anchorage independent growth , and by constructing mutational variants of T antigen we showed that binding of large T antigen to p 53 and RB was necessary to induce anchorage independent growth . ^^^ Although c abl / p53 double knockout MEFs did not undergo anchorage independent growth , those expressing human papilloma virus 16 E 7 , which mainly inactivates RB , did . ^^^ Our results show that the loss of c abl facilitates anchorage independent growth in the context of p 53 and RB deficiency , and suggest that loss of function of c abl facilitates some types of transformation . . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| To evaluate the frequency of cytogenetically undetectable abnormalities , we performed fluorescence in situ hybridization ( FISH ) analyses in 273 AML M 0 M2 with normal karyotype using probes for ETO , ABL , MLL , TEL , RB , P 53 , AML 1 , and BCR . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| Rb inhibits the Abl tyrosine kinase . ^^^ Thus , Rb inactivation is a pre requisite for Abl activation by DNA damage or TNF . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| RB resistant Abl kinase induces delayed cell cycle progression and increases susceptibility to apoptosis upon cellular stresses through interaction with p 53 . c Abl , a non receptor tyrosine kinase , is found in both nucleus and cytoplasm of proliferating fibroblasts . ^^^ RB negatively regulates the kinase activity of c Abl . ^^^ Overexpression of kinase active c Abl can overcome RB induced growth arrest in Saos 2 cells . ^^^ In this study , we investigated whether overexpression of mutant c Abl ( AS 2 , RB resistant Abl kinase ) not only lead to delayed cell cycle progression but also make cells susceptible to apoptosis under coexpression with a fragment of RB C pocket in human skin fibroblast . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| Nine of these genes ( H ras , c myc , c fos , c jun , junB , N myc , c abl , c yes , and p 53 ) were expressed in epithelial cells , whereas two ( RB 1 and N ras ) were not . expression of four other genes ( c src , K ras , c raf , and c myb ) was observed , but the intensity of these bands was too low for densitometric analysis . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| Molecular genetic abnormalities preceding , or occurring during , BC include overexpression of the BCR / ABL transcript , upregulation of the EVI 1 gene , increased telomerase activity , and mutations of the tumor suppressor genes RB 1 , TP 53 , and CDKN2A . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| The nuclear arrangement of the ABL , c MYC , and RB 1 genes was quantitatively investigated in human undifferentiated HL 60 cells and in a terminally differentiated population of human granulocytes . ^^^ The ABL gene was expressed in both cell types , the c MYC gene was active in HL 60 cells and down regulated in granulocytes , and expression of the RB 1 gene was undetectable in HL 60 cells but up regulated in granulocytes . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| Rb plays a role in survival of Abl dependent human tumor cells as a downstream effector of Abl tyrosine kinase . ^^^ Although Rb is known to be an upstream negative regulator of Abl protein tyrosine kinase , we propose here that Rb also functions as a downstream effector of Abl that plays a positive role in survival of Abl dependent human tumor cells , including Bcr / Abl positive chronic myelogenous leukemia ( CML ) . ^^^ We show that Rb is constitutively phosphorylated at tyrosine in Abl dependent tumor cells , and that Abl phosphorylates Rb specifically at Y 805 within the C terminal domain of the molecule . ^^^ We also show that ectopic expression of Rb induces apoptosis in Abl dependent tumor cells by inhibiting the Abl tyrosine kinase activity , and that Rb induced apoptosis is compromised by Abl catalysed phosphorylation of Rb at Y 805 . ^^^ Furthermore , the silencing of endogenous Rb by RNA interference induced apoptosis in Abl dependent tumor cells . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| PIN 1 , FEN 1 , and cABL up regulation and LMNB 1 , AREG , RhoB , CCNG , TYMS , F 3 , and MGMT down regulation suggest that methionine stress sensitizes the tumor cells to DNA alkylating drugs , 5 fluorouracil , and radiation . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| The study of these events led to the identification of the key genes involved ( BCR , ABL , C MYC , RB 1 and N MYC ) and served as models for substantial further work . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| We have investigated the involvement of tumor suppressor genes ( p 53 and RB 1 ) and dominantly acting oncogenes ( Ras family genes ) in BCR / ABL positive and negative chronic myeloproliferative disorders ( CMPD ) at different stages of the disease , including 26 cases of BCR / ABL+ chronic myeloid leukemia ( CML ) blast crisis , 9 myelosclerosis with myeloid metaplasia , 4 polycythemia vera , 10 essential thrombocythemia , 1 juvenile CML , and 8 BCR / ABL CML . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| For FISH the following probes were used : MLL , CBF beta / MYH11 , ETV 6 / AML1 ; AML1 / ETO , BCR / ABL , PML / RAR , c MYC , TP 53 , RB 1 , 5q31 / 5p15 . 2 , 5q33 34 , 7q31 / CEP7 , 20q13 ; CEP 4 , 10 , Y . ^^^ |
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| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| RESULTS : Seventeen genes ( ABL , APC , APAF 1 , BRCA 1 , CSPG 2 , DAPK 1 , hMLH 1 , LKB 1 , PTEN , p14ARF , p15INK4b , p27KIP1 , p57KIP2 , RASSF1C , RB 1 , SURVIVIN , and VHL ) displayed a uniformly unmethylated pattern in all the astrocytoma and non astrocytoma tissues examined . ^^^ |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P06400 and P00519 |
Pubmed |
SVM Score :0.0 |
| NA |
|