1996
DOI: 10.1101/gad.10.23.2960
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Degradation of E2F by the ubiquitin-proteasome pathway: regulation by retinoblastoma family proteins and adenovirus transforming proteins.

Abstract: E2F transcription factors are key regulators of transcription during the cell cycle. E2F activity is regulated at the level of transcription and DNA binding and by complex formation with the retinoblastoma pocket protein family. We show here that free E2F-1 and E2F-4 transcription factors are unstable and that their degradation is mediated by the ubiquitin-proteasome pathway. Both E2F-I and E2F-4 are rendered unstable by an epitope in the carboxyl terminus of the proteins, in close proximity to their pocket pr… Show more

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Cited by 197 publications
(167 citation statements)
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“…Evidence from several studies indicate that there are cytoplasmic factors that p21 can deactivate to inhibit apoptosis including ASK1 (apoptosis signal -regulating kinase 1) and caspase-3. 47,49 Interestingly, recent data indicate that treatment with the chemotherapeutic drug, camptothecin, results in caspase -mediated cleavage of p21 resulting in the production of a 15-kDa N -terminal fragment of p21 that does not bind to PCNA. 37 The cleavage of p21 results in the conversion of cancer cells from growth arrest to apoptosis and is thought to be a critical step in the acceleration of chemotherapyinduced tumor cell death.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Evidence from several studies indicate that there are cytoplasmic factors that p21 can deactivate to inhibit apoptosis including ASK1 (apoptosis signal -regulating kinase 1) and caspase-3. 47,49 Interestingly, recent data indicate that treatment with the chemotherapeutic drug, camptothecin, results in caspase -mediated cleavage of p21 resulting in the production of a 15-kDa N -terminal fragment of p21 that does not bind to PCNA. 37 The cleavage of p21 results in the conversion of cancer cells from growth arrest to apoptosis and is thought to be a critical step in the acceleration of chemotherapyinduced tumor cell death.…”
Section: Discussionmentioning
confidence: 99%
“…47 Therefore, we suspected that protein stability might be a factor related to the altered expression of E2F -1 in the combination therapies. E2F -1 protein half -life was measured by determining the level of protein at various time points following treatment with the protein synthesis inhibitor, cycloheximide.…”
Section: Cell Death Is Due To Apoptosismentioning
confidence: 99%
“…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%
“…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%