A novel mitochondrial protein DIP mediates E2F1-induced apoptosis independently of p53.
Cell Death Differ
; 12(4): 347-57, 2005 Apr.
Article
in En
| MEDLINE
| ID: mdl-15565177
ABSTRACT
The transcription factor E2F1 does not only induce cell proliferation but also shows the strongest proapoptotic effect of all E2F family members as part of an antitumor safeguard mechanism. We have recently identified KIAA0767 as a novel p53-independent target of E2F1. Here, we investigated the biological function of interaction. Overexpression studies of KIAA0767, termed D(eath)-I(nducing)-P(rotein), revealed its strong proapoptotic effect. DIP greatly reduced cell viability in several in vitro systems accompanied by typical apoptotic features such as caspase-3 activation and cleavage of poly(ADP-ribose)-polymerase. Endogenous DIP levels increased following E2F1 activation. Yet, inhibition of endogenous DIP function by small interfering RNA rescued p53-negative cells from E2F1-induced apoptosis, indicating that DIP is an essential mediator of the p53-independent E2F1 death pathway. Localization studies showed that DIP localizes to the mitochondria, where endogenous DIP is upregulated following E2F1 induction. These results provide new insights to the incompletely understood regulatory mechanisms of E2F1-induced apoptosis.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Tumor Suppressor Protein p53
/
Apoptosis
/
Cell Cycle Proteins
/
Mitochondrial Proteins
/
DNA-Binding Proteins
/
Mitochondria
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Cell Death Differ
Year:
2005
Type:
Article
Affiliation country:
Germany