The retinoblastoma gene product protects E2F-1 from degradation by the ubiquitin-proteasome pathway - PubMed (original) (raw)
. 1996 Dec 1;10(23):2949-59.
doi: 10.1101/gad.10.23.2949.
Affiliations
- PMID: 8956996
- DOI: 10.1101/gad.10.23.2949
Free article
The retinoblastoma gene product protects E2F-1 from degradation by the ubiquitin-proteasome pathway
F Hofmann et al. Genes Dev. 1996.
Free article
Abstract
E2F-1 plays a crucial role in the regulation of cell-cycle progression at the G1-S transition. In keeping with the fact that, when overproduced, it is both an oncoprotein and a potent inducer of apoptosis, its transcriptional activity is subject to multiple controls. Among them are binding by the retinoblastoma gene product (pRb), activation by cdk3, and S-phase-dependent down-regulation of DNA-binding capacity by cyclin A-dependent kinase. Here we report that E2F-1 is actively degraded by the ubiquitin-proteasome pathway. Efficient degradation depends on the availability of selected E2F-1 sequences. Unphosphorylated pRb stabilized E2F-1, protecting it from in vivo degradation. pRb-mediated stabilization was not an indirect consequence of G1 arrest, but rather depended on the ability of pRb to interact physically with E2F-1. Thus, in addition to binding E2F-1 and transforming it into a transcriptional repressor, pRb has another function, protection of E2F-1 from efficient degradation during a period when pRb/E2F complex formation is essential to regulating the cell cycle. In addition, there may be a specific mechanism for limiting free E2F-1 levels, failure of which could compromise cell survival and/or homeostasis.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources