| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.88724577 |
| Here we show that geminin interacts tightly with Cdt 1 , a recently identified replication initiation factor necessary for MCM loading . 0.88724577^^^ |
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| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.8525824 |
| MCM 6 interacts with the Cdt 1 carboxyl terminal region ( amino acids 407 477 ) , which is conserved among eukaryotes , whereas geminin associates with the Cdt 1 central region ( amino acids 177 380 ) , which is conserved only in metazoans . 0.8525824^^^ We found by yeast two hybrid analysis that mouse Cdt 1 associates with geminin , MCM 6 , and origin recognition complex 2 . 0.72794752^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.77332222 |
| Published evidence shows that geminin specifically interacts with Cdt 1 to block its function in the assembly of prereplication complexes . 0.77332222^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.5593905 |
| Geminin binds tightly to Cdt 1 , an essential component of the replication licensing system , and prevents the inappropriate reinitiation of replication on an already fired origin . 0.5593905^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.7303526 |
| Only the central region binds geminin tightly enough to successfully compete with full length Cdt 1 for geminin binding . 0.7303526^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.61365741 |
| After DNA replication is initiated during a cell cycle , geminin binds to Cdt 1 , one of the key DNA replication licensing factors . 0.61365741^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| All these deficits were rescued by overexpression of Cdt 1 , a replication initiator protein that binds to Geminin . ^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Geminin binds to Cdt 1 to ensure that DNA replication occurs only once during the cell cycle . ^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Geminin inhibits DNA replication by preventing Cdt 1 from loading minichromosome maintenance ( MCM ) proteins onto DNA . ^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Overexpression of Dm geminin in embryos inhibits DNA replication , but cells enter mitosis arresting in metaphase , as in dup ( cdt 1 ) mutants , and undergo apoptosis . ^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| To investigate the functional significance of this binding , nuclei prepared from CHO cells synchronized at various times after metaphase were introduced into Xenopus egg extracts , which were either immunodepleted of Mcm proteins or supplemented with geminin , an inhibitor of the Mcm loading protein Cdt 1 . ^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| The effect of geminin deficiency is completely suppressed by cosilencing of Double parked ( Dup ) , the Drosophila homologue of Cdt 1 , a replication factor to which geminin binds . ^^^ We observed that the silencing of geminin causes rapid downregulation of Cdt1 / Dup , which may contribute to the observed partial overreplication in geminin deficient cells . ^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Geminin , whose degradation at the end of mitosis is essential for a new round of licensing , has been shown to bind Cdt 1 and negatively regulate it , providing a new insight into the regulation of DNA replication in higher eukaryotes . . ^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Regulation of CDC 6 , geminin , and CDT 1 in human cells that undergo polyploidization . ^^^ Cdc 6 , cdt 1 , and geminin expression was analyzed during differentiation of two human megakaryoblastic cell lines , HEL and K 562 , which respectively do and do not establish endoreplication cycles . ^^^ Geminin was downregulated , whereas cdt 1 levels were maintained upon differentiation of both cell lines , independently of whether cells entered extra S phases . ^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Cdt 1 activity is inhibited by the geminin protein , and we provide evidence that the mechanism of this inhibition involves blocking the binding of Cdt 1 to both Mcm 2 and Cdc 6 . ^^^ These results identify novel molecular functions for both Cdc 6 and geminin in controlling the association of Cdt 1 with other components of the replication apparatus and indicate that the association of Cdt 1 with the Mcm complex is controlled as cells exit and reenter the cell cycle . . ^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Geminin inhibits cell cycle progression by sequestering Cdt 1 ( refs 4 , 5 ) , the key component for the assembly of the pre replication complex . ^^^ Here , we show that Six 3 efficiently competes with Cdt 1 directly to bind to geminin , which reveals how Six 3 can promote cell proliferation without transcription . ^^^ |
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| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Regulation of Geminin and Cdt 1 expression by E2F transcription factors . ^^^ Geminin and Cdt 1 play an essential role in the initiation of DNA replication , by regulating the chromatin loading of the MCM complex . ^^^ In this study , we showed that the transcription of human Geminin and Cdt 1 , as well as that of MCM 7 , is activated by transcription factors E2F1 4 , but not by factors E2F5 7 . ^^^ Analysis of various Geminin and Cdt 1 promoter constructs showed that an E2F responsive sequence in the vicinity of the transcription initiation site is necessary for the transcriptional activation . ^^^ Furthermore , the promoter activities of human Geminin and Cdt 1 were demonstrated to be growth dependent . ^^^ |
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| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Cdt 1 phosphorylation by cyclin A dependent kinases negatively regulates its function without affecting geminin binding . ^^^ It has been suggested in metazoan cells that the function of Cdt 1 is blocked through binding to an inhibitor protein , geminin . ^^^ However , the functional relationship between the Cdt 1 geminin system and Cdks remains to be clarified . ^^^ However , geminin binding to Cdt 1 was not affected by the phosphorylation . ^^^ Taken together , these findings suggest that Cdt 1 function is also negatively regulated by the Cdk phosphorylation independent of geminin binding . . ^^^ |
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| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| The activity of Cdt 1 is inhibited by geminin . ^^^ The mechanism by which geminin interferes with Cdt 1 activity is unknown . ^^^ It is thought that geminin binds to and sequestrate Cdt 1 . ^^^ We show that geminin does not interfere with the chromatin association of Cdt 1 and that inhibition of DNA synthesis by geminin is observed following its accumulation on chromatin . ^^^ We demonstrate that loading of geminin onto chromatin requires Cdt 1 , suggesting that geminin is targeted at replication origins . ^^^ |
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| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Human geminin promotes pre RC formation and DNA replication by stabilizing CDT 1 in mitosis . ^^^ Geminin is an unstable inhibitor of DNA replication that negatively regulates the licensing factor CDT 1 and inhibits pre replicative complex ( pre RC ) formation in Xenopus egg extracts . ^^^ We demonstrate that human Geminin protects CDT 1 from proteasome mediated degradation by inhibiting its ubiquitination . ^^^ In particular , Geminin ensures basal levels of CDT 1 during S phase and its accumulation during mitosis . ^^^ Taken together with recent data from our laboratory , our results demonstrate that Geminin is both a negative and positive regulator of pre RC formation in human cells , playing a positive role in allowing CDT 1 accumulation in G 2 M , and preventing relicensing of origins in S G2 . . ^^^ |
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| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Cdt 1 and geminin are down regulated upon cell cycle exit and are over expressed in cancer derived cell lines . ^^^ Cdt 1 was recently discovered as an essential licensing factor , which is inhibited by geminin . ^^^ Cdt 1 ' s inhibitor , geminin , is similarly down regulated upon cell cycle exit at both the protein and RNA level , and geminin protein accumulates with a 3 6 h delay over Cdt 1 , following serum re addition . ^^^ Similarly , mouse NIH3T3 cells down regulate Cdt 1 and geminin mRNA and protein when serum starved . ^^^ Our data suggest a transcriptional control over Cdt 1 and geminin at the transition from quiescence to proliferation . ^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Geminin has dimerization , Cdt 1 binding , and destruction domains that are required for biological activity . ^^^ Geminin inhibits a second round of DNA synthesis during S and G ( 2 ) phase by binding the essential replication protein Cdt 1 . ^^^ Geminin ' s Cdt 1 binding domain lies immediately adjacent to the dimerization domain and overlaps it . ^^^ We identified several missense mutations in geminin ' s Cdt 1 binding domain that were deficient in their ability to inhibit replication yet were still able to allow mitotic entry , suggesting that these are separate functions of geminin . . ^^^ |
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| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| We have investigated regulation of the origin licensing factors Cdc 6 , Cdt 1 , Mcm 2 and Geminin in human somatic and germ cells . ^^^ In striking contrast , we show that proliferation control during male gametogenesis is not linked to Cdc 6 or Mcm 2 , but appears to be coordinated by the negative regulator Geminin with Cdt 1 becoming rate limiting in late prophase . ^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| One inhibitor of pre RC assembly , geminin , was discovered in Xenopus , and it binds and inactivates Cdt 1 in S phase . ^^^ When fresh Cdt 1 is supplied after the first round of DNA replication , significant rereplication results , and rereplication is enhanced in the absence of geminin . ^^^ Our results identify a replication dependent proteolytic pathway that targets Cdt 1 and that acts redundantly with geminin to inactivate Cdt 1 in S phase . . ^^^ |
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| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Geminin Cdt 1 balance is critical for genetic stability . ^^^ Higher eukaryotes have evolved another redundant mechanism , an inhibitor called geminin , to restrain Cdt 1 activity . ^^^ This review proposes that a balance between Cdt 1 and geminin is important for maintaining genomic stability . . ^^^ |
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| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Cdt 1 downregulation by proteolysis and geminin inhibition prevents DNA re replication in Xenopus . ^^^ We show that Cdt 1 is downregulated late in the cell cycle by two different mechanisms : proteolysis , which occurs in part due to the activity of the anaphase promoting complex ( APC / C ) , and inhibition by a protein called geminin . ^^^ |
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| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Reinitiation is blocked by geminin only in G 2 and is not stimulated by Cdc 6 , demonstrating that Cdt 1 , but not Cdc 6 , is limiting for reinitiation in egg extracts . ^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Geminin , a metazoan specific inhibitor of Cdt 1 , was critical for preventing re replication induced by Cdt 1 . ^^^ Re replication induced by the addition of recombinant Cdt 1 and / or by the depletion of geminin from extracts was enhanced by a proteasome inhibitor , which suppressed the degradation of Cdt 1 in the extracts . ^^^ Furthermore , a nuclear localization sequence identified in Xenopus geminin had a significant role in the suppression of re replication induced by Cdt 1 . ^^^ |
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| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Cdt 1 activity is inhibited by geminin , which also participates in neural development and embryonic differentiation in many eukaryotes . ^^^ Although Cdt 1 homologues have been identified in organisms ranging from yeast to human , geminin homologues had not been described for Caenorhabditis elegans and fungi . ^^^ We conclude that the Cdt 1 geminin system is conserved throughout metazoans and that geminin has evolved in these taxa to regulate proliferation and differentiation by directly interacting with Cdt 1 and homeobox proteins . . ^^^ |
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| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Cdt 1 is an essential component of the pre RC that is rapidly degraded at G 1 S and also inhibited by Geminin ( Gem ) protein to prevent re replication . ^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Geminin inhibits pre replication complex assembly by preventing Cdt 1 from recruiting the minichromosome maintenance proteins to chromatin . ^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| In the forebrain of medaka embryos , Six 3 facilitates cellular proliferation by sequestration of Geminin from Cdt 1 , a key component in the assembly of the prereplication complex . ^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Expression of the licensing factors , Cdt 1 and Geminin , in human colon cancer . ^^^ Cdt 1 was recently discovered as an important licensing factor , that is inhibited by Geminin . ^^^ In the present study we analyzed Cdt 1 and Geminin expression in human colon cancer . ^^^ Similarly , Geminin , Cdt 1 ' s inhibitor , is also overexpressed in colon carcinomas and its expression correlates with significant clinicopathological parameters of the disease . ^^^ Moreover , both Cdt 1 and Geminin expression are severely downregulated upon differentiation of Caco 2 cells , an in vitro model of intestinal epithelial differentiation . . ^^^ |
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| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Cdt 1 , a protein essential in G 1 for licensing of origins for DNA replication , is inhibited in S phase , both by binding to geminin and degradation by proteasomes . ^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| While both cell types showed increased cytoplasmic geminin , the DNA synthesis initiating protein Cdt 1 was predominantly nuclear in PAEC but remained cytoplasmic in A 549 cells , consistent with the stimulation of DNA synthesis in the former but an inhibition in the latter cell type . ^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Several mechanisms of pre RC regulation are known , including ATP utilization , cyclin dependent kinase levels , protein turnover , and Cdt 1 binding by geminin . ^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| In higher eukaryotes , regulation of the licensing factor Cdt 1 by proteolysis and Geminin is essential to prevent re replication . ^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| Interestingly , DNA binding of ORC , CDC 6 , and CDT 1 was significantly stabilized in the presence of geminin , under which conditions approximately 10 20 molecules each of ORC and CDC 6 were bound . ^^^ |
|
| Interacting proteins: O75496 and Q9H211 |
Pubmed |
SVM Score :0.0 |
| These included a link to Crm 1 dependent nuclear export and the observation that Cdt 1 , a protein in the pre replication complex , could also mediate nuclear import of Gem . ^^^ |
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