REGULATION OF E2F THROUGH UBIQUITIN-PROTEASOME-DEPENDENT DEGRADATION - STABILIZATION BY THE PRB TUMOR-SUPPRESSOR PROTEIN

The E2F family of transcription factors plays a key role in regulating cell-cycle progression, Accordingly, E2F is itself tightly controlled by a series of transcriptional and posttranscriptional events, Here w e provide evidence that E2F1 protein levels are regulated by the ubiqu itin-proteasome-dependent degradation pathway, An analysis of E2F1 mut ants identified a conserved carboxyl-terminal region, which is require d for eliciting ubiquitination and protein turnover, Fusion of this E2 F1 carboxyl-terminal sequence to a heterologous protein, GAL4, resulte d in destabilization of GAL4. Previous studies identified an overlappi ng region of E2F1 that facilitates complex formation with retinoblasto ma tumor suppressor protein, pRB, and we found that pRB blocks ubiquit ination and stabilizes E2F1, These results suggest a new mechanism for controlling the cell-cycle regulatory activity of E2F1.