The retinoblastoma gene product protects E2F-1 from degradation by the ubiquitin-proteasome pathway.

Hofmann, Francesco; Martelli, Fabio; Livingston, David M.; Wang, Zhiyan

doi:10.1101/gad.10.23.2949

Cited by 225 publications

(213 citation statements)

References 62 publications

Supporting

Mentioning

190

Contrasting

Unclassified

Order By: Relevance

“…The expression of E2F1 and pRb was confirmed by Western blot analysis (top panel in Figure 1A, panel A3). Of note, pRb could stabilize the protein level of E2F1 (top panel in Figure 1A, panel A3), which is consistent with previous reports [33][34][35]. In addition, the E2F1 mutant [E2F1(E132)] lacking DNA-binding activity failed to transactivate pVHL promoter activity ( Figure 1A, panel A4), which suggested that the DNA-binding activity of E2F1 was required for activating pVHL.…”

Section: Results Pvhl Is a Direct Downstream Target Of E2f1supporting

confidence: 89%

pVHL acts as a downstream target of E2F1 to suppress E2F1 activity

Wang

Zhang

et al. 2013

Biochemical Journal

View full text Add to dashboard Cite

The VHL (von Hippel-Lindau) gene is a well-defined tumour suppressor linked to hereditary cancer syndromes. Although it is well documented that pVHL (von Hippel-Lindau protein) mediates HIF (hypoxia-inducible factor)-1/2α degradation under conditions of normoxia, accounting for a major mechanism of pVHL in tumour suppression, it remains elusive whether other HIF-independent functions contribute to the pVHL tumour suppressive function. In the present study, we found that pVHL is a downstream target of E2F1, which harbours an E2F1-binding site in its promoter. Moreover, pVHL binds to E2F1 in vitro and in vivo, resulting in inhibition of E2F1 transcriptional activity. Mechanistic studies showed that pVHL binding enhances E2F1 deacetylation. Further immunoprecipitation assays indicated that the pVHL interaction diminishes P/CAF [p300/CREB (cAMPresponse-element-binding protein)-binding protein-associated factor] and p300 association with E2F1, but enhances Sirt1 (sirtuin 1) binding to E2F1. In addition, upon DNA damage, pVHL is induced. Knockdown of pVHL sensitizes cells to DNA-damageinduced apoptosis dependent on E2F1, uncovering a role for pVHL in the response to DNA damage. The findings of the present study reveal a novel function of pVHL and demonstrate a negative-feedback loop between pVHL and E2F1, which may shed new light on the explanation of the role of pVHL in tumour suppression.

show abstract

Section: Results Pvhl Is a Direct Downstream Target Of E2f1supporting

confidence: 89%

pVHL acts as a downstream target of E2F1 to suppress E2F1 activity

Wang

Zhang

et al. 2013

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…Alternatively, Rb may compete with some other proteins involved in the degradation pathway which bind to the same or similar sites of mdm2 to mediate its ability to target p53 for degradation (Figure 1). The ability of Rb to prevent protein degradation through proteinprotein interaction has been demonstrated with E2F1 (Campanero and Flemington, 1997;Hateboer et al, 1996;Hofmann et al, 1996). Whether common mechanisms exist for Rb in preventing protein degradation remain to be seen.…”

Section: Rb Apoptosismentioning

confidence: 99%

mdm2: a bridge over the two tumour suppressors, p53 and Rb

et al. 1999

View full text Add to dashboard Cite

The inactivation of the p53 and Rb pathways would account for the majority of human tumours. There are many levels of cross talk between p53 and Rb that have been identi®ed. However, the identi®cation of the mdm2-Rb interaction established a closer link between the two most well studied tumour suppressors, p53 and Rb. Recent studies of the novel trimeric complex Rb-mdm2-p53 provided us with a functional insight of how the two tumour suppressors can act together in regulating p53 induced apoptosis. Beginning with the properties of the Rb-mdm2-p53 trimeric complex, we shall review the propounding evidence suggesting that the apoptotic function of p53 is linked to its transrepression function. The uncoupling of the apoptotic function and transactivation function of p53 will also be discussed.

show abstract

“…Previous work in which E2F proteins were highly overexpressed by transient transfection have demonstrated that E2F-1 and E2F-4 have the potential to be degraded by the ubiquitin ± proteosome pathway (Hateboer et al, 1996;Hofmann et al, 1996). It is quite possible that the rapid degradation of E2F-3 in cell cycle stages other than S phase is mediated by the ubiquitin ± proteosome pathway.…”

Section: The Half-life Of E2f-3 Increases During S Phasementioning

confidence: 99%

E2F-3 accumulation is regulated by polypeptide stability

1998

Oncogene

View full text Add to dashboard Cite

E2F is a complex family of transcription factors which appears to regulate the transcription of genes required for the S phase of the mammalian cell cycle. In the present work, we have examined the mechanisms regulating E2F-3 accumulation in mouse ®broblasts. We have determined that E2F-3 DNA binding activity is restricted to the G 1 /S transition and S phase in both normal BALB/c-3T3 ®broblasts and in an SV40 virustransformed BALB/c-3T3 derivative. Immunoblot analysis indicates that G 0 and G 1 cells have little or no E2F-3 polypeptide and that the increase in the DNA binding activity of E2F-3 at the G 1 /S boundary is re¯ected by an increase in total E2F-3 protein. In contrast to the E2F-3 polypeptide, RNAse protection assays demonstrate that the E2F-3 mRNA is clearly present in G 0 and G 1 cells. Finally, pulse/chase experiments indicate that the halflife of E2F-3 is approximately 40-fold greater in cells blocked in S phase relative to asynchronously growing cells. Together, these results indicate that the accumulation E2F-3 at S phase may be regulated, at least in part, at the level of protein stability.

show abstract

The retinoblastoma gene product protects E2F-1 from degradation by the ubiquitin-proteasome pathway.

Cited by 225 publications

References 62 publications

pVHL acts as a downstream target of E2F1 to suppress E2F1 activity

pVHL acts as a downstream target of E2F1 to suppress E2F1 activity

mdm2: a bridge over the two tumour suppressors, p53 and Rb

E2F-3 accumulation is regulated by polypeptide stability

Contact Info

Product

Resources

About