The retinoblastoma protein copurifies with E2F-I, an E1A-regulated inhibitor of the transcription factor E2F

Bagchi, Srilata; Weinmann, Roberto; Raychaudhuri, Pradip

doi:10.1016/0092-8674(91)90558-g

Cited by 430 publications

(235 citation statements)

References 49 publications

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“…Furthermore, Rb has been reported to interact with several cyclins including A, D and E (Hinds et al, 1992;Matsushime et al, 1992) as well as the transcriptional activator E2F (Bagchi et al, 1991;Chellappan et al, 1991) and MDM2 (Xiao et al, 1995). Evidence has been provided indicating that Rb plays an active role in antagonizing the death response (Ewen, 1994).…”

Section: Degradation Of Rb Following Tnf Adwtp53 Treatment Of Tnf-resmentioning

confidence: 99%

Adenovirus-mediated transfer of wild-type p53 gene sensitizes TNF resistant MCF7 derivatives to the cytotoxic effect of this cytokine: relationship with c-myc and Rb

et al. 1999

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Tumor suppressor p53 is a nuclear transcription factor that blocks cell cycle progression and induces apoptosis. We have previously shown that the MCF7 resistance to the cytotoxic action of TNF correlates with p53 mutations. In the present study, we used a recombinant adenovirus carrying a wild-type p53 gene (Adwtp53) in order to investigate the e ect of wt p53 transfer on modulation of cell resistance to the cytotoxic action of TNF. Our data indicate that infection of TNF resistant MCF7 cells (1001 and MCF7/Adr) with Adwtp53 resulted in the restoration of wt p53 expression and function as respectively revealed by the yeast assay and the induction of p53 inducible genes MDM2 and p21. Furthermore, the restoration of p53 function signi®cantly sensitized TNF resistant cells to TNF cytotoxic action. This correlated with a signi®cant down-regulation of cmyc in both TNF-resistant cell lines and a decrease of Retinoblastoma protein (Rb) in 1001 clone. In contrast, the e ect of p53 seems to be independent from Bcl-2 and Bax protein level regulation. The present study suggests that the combination of TNF and Adwtp53 may be a potential strategy to sensitize mutant p53 TNF-resistant tumors to the cytotoxic action of this cytokine.

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Section: Degradation Of Rb Following Tnf Adwtp53 Treatment Of Tnf-resmentioning

confidence: 99%

Adenovirus-mediated transfer of wild-type p53 gene sensitizes TNF resistant MCF7 derivatives to the cytotoxic effect of this cytokine: relationship with c-myc and Rb

et al. 1999

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“…The p107 and p130 protein levels decreased somewhat at 20 and 30 weeks of promotion, the decrease in p130 being more notable ( Figure 5). E2F transcription factors have been implicated as critical targets for the tumor suppressor pRb and pRbrelated proteins (Bagchi et al, 1991;Bandara et al, 1991;Chellappan et al, 1991). Five members of the E2F family have been described (E2F-1 to E2F-5) but only E2F-1 has been associated with tumorigenesis (Johnson et al, 1994;Singh et al, 1994;Yamasaki et al, 1996).…”

Section: Expression Of Rb Family Proteins and E2f Transcription Factorsmentioning

confidence: 99%

“…Loss of Rb function contributes to the loss of cell growth control in various tumors (Weinberg, 1991). There is considerable evidence that the E2F transcription factors are a critical target for pRb and pRb-related proteins (Bagchi et al, 1991;Bandara et al, 1991;Chellappan et al, 1991). The interaction of pRb with E2F correlates with the capacity of pRb to arrest cell growth in G1 phase (Hiebert, 1993;Hiebert et al, 1992;Qian et al, 1992;Qin et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Deregulated expression of cell-cycle proteins during premalignant progression in SENCAR mouse skin

et al. 1998

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It is now evident that several genes encoding regulatory activities that control the mammalian cell cycle, particularly some that control the progression of quiescent cells through G1 and into S phase, are targets for alterations that underlie the development of neoplasms. Here, we made a sequential study of alterations in cell cycle protein expression and complex formation among cyclin, cyclin dependent kinases (CDKs) and CDK inhibitors (CKIs) during premalignant progression in SENCAR mouse skin tumors. Changes in the level of expression were observed in positive (cyclin D1, D2, and E2F family members) and negative regulators (p16 Ink4a , p57 Kip2 ) of the cell cycle. Also, we observed the formation of cyclin/CDK/CKI complexes. The amounts of these proteins and complexes increased substantially at speci®c times during promotion but not during malignant conversion to carcinomas. These data show that deregulation of growth control occurs in benign tumors and that subsequent mutations not involved cell-cycle regulation are probably necessary to induce invasive behavior.

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“…This transition is controlled by G 1 cyclins, including D and E type cyclins and their cyclin-dependent kinases (cdks), whose phosphorylation of the retinoblastoma gene product (pRB) and pRB-related proteins facilitates entry into S phase (Sherr, 1994). Hypophosphorylated pRB has been shown to bind the transcription factor E2F resulting in an inhibition of E2F-dependent transcription (Bagchi et al, 1991;Chellappan et al, 1991;Chittenden et al, 1991). This repression is relieved following phosphorylation of pRB by the G 1 cyclindependent kinases (Hinds et al, 1992;Dowdy et al, 1993;Ewen et al, 1993;Kato et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Regulated ectopic expression of cyclin D1 induces transcriptional activation of the cdk inhibitor p21 gene without altering cell cycle progression

et al. 1997

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Cyclin D1 plays a key regulatory role during the G 1 phase of the cell cycle and its gene is ampli®ed and overexpressed in many cancers. To address the relationship between cyclin D1 and other cell cycle regulatory proteins, we established human glioma and rodent ®broblast cell lines in which cyclin D1 expression could be regulated ectopically with tetracycline. In both of these cell lines, we found that ectopic expression of cyclin D1 in asynchronously growing cells was accompanied by increased levels of the p53 tumor suppressor protein and the cyclin/cdk inhibitor p21. Despite the induction of these cell cycle inhibitory proteins, cyclin D1-associated cdk kinase remained activated and the cells grew essentially like that of the parent cells. Although growth parameters were unchanged in these cells, morphological changes were clearly identi®able and anchorage independent growth was observed in NIH3T3 cells. In a ®rst step toward elaborating the mechanism for cyclin D1-mediated induction of p21 gene expression we show that co-expression of E2F-1 and DP-1 can speci®cally transactivate the p21 promoter. In support of these ®ndings and a direct e ect of E2F on induction of p21 gene expression a putative E2F binding site was identi®ed within the p21 promoter. In summary, our results demonstrate that ectopic expression of cyclin D1 can induce gene expression of the cdk inhibitor p21 through an E2F mechanism the consequences of which are not to growth arrest cells but possibly to stabilize cyclin D1/cdk function.

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The retinoblastoma protein copurifies with E2F-I, an E1A-regulated inhibitor of the transcription factor E2F

Cited by 430 publications

References 49 publications

Adenovirus-mediated transfer of wild-type p53 gene sensitizes TNF resistant MCF7 derivatives to the cytotoxic effect of this cytokine: relationship with c-myc and Rb

Adenovirus-mediated transfer of wild-type p53 gene sensitizes TNF resistant MCF7 derivatives to the cytotoxic effect of this cytokine: relationship with c-myc and Rb

Deregulated expression of cell-cycle proteins during premalignant progression in SENCAR mouse skin

Regulated ectopic expression of cyclin D1 induces transcriptional activation of the cdk inhibitor p21 gene without altering cell cycle progression

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