Jab1 is a specificity factor for E2F1-induced apoptosis.
The members of the E2F family of transcription factors are key regulators of genes involved in cell cycle progression, cell fate determination, DNA damage repair, and apoptosis. Many cell-based experiments suggest that E2F1 is a stronger inducer of apoptosis than the other E2Fs. Our previous work identified the E2F1 marked box and flanking region as critical for the specificity in E2F1 apoptosis induction. We have now used a yeast two-hybrid screen to identify proteins that bind the E2F1 marked box and flanking regions, with a potential role in E2F1 apoptosis induction. We identified Jab1 as an E2F1-specific binding protein and showed that Jab1 and E2F1 coexpression synergistically induce apoptosis, coincident with an induction of p53 protein accumulation. In contrast, Jab1 does not synergize with E2F1 to promote cell cycle entry. Cells depleted of Jab1 are deficient for both E2F1-induced apoptosis and induction of p53 accumulation. We suggest that Jab1 is an essential cofactor for the apoptotic function of E2F1.
Duke Institute for Genome Sciences and Policy Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Timothy C
TC
Hallstrom
Joseph R
JR
Nevins
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis / Q000502:physiology*; D000075686:COP9 Signalosome Complex; D002460:Cell Line; D004249:DNA Damage; D050687:E2F1 Transcription Factor / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D010447:Peptide Hydrolases / Q000378:metabolism / Q000502:physiology*; D011233:Precipitin Tests; D011485:Protein Binding; D012680:Sensitivity and Specificity; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D050687:E2F1 Transcription Factor; D047908:Intracellular Signaling Peptides and Proteins; D016159:Tumor Suppressor Protein p53; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex