Abstract
The human ARF/INK4a locus encodes two cell cycle inhibitors, p16INK4a and p14ARF, by using separate promoters. A variety of mitogenic stimuli upregulate ARF but a direct modulation at the transcriptional level has been reported only for E2F-1. We show here that the ARF promoter is strongly responsive also to E2F2 and E2F3, thus providing a strong support to their suggested role in the induction of apoptosis. Through the usage of both deletion mutants and/or site-directed mutants, we surprisingly found that none of the four putative E2F consensus sites is strictly necessary for the upregulation of ARF expression, as a minimal deletion mutant, lacking all the putative E2F binding sites, is still transactivated by E2F. Moreover, our data suggest that the ARF promoter is regulated by E2F through both direct binding to the promoter sequences and indirectly, probably by being tethered to the ARF promoter by Sp1-like factors.
Original language | English (US) |
---|---|
Pages (from-to) | 1138-1145 |
Number of pages | 8 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 291 |
Issue number | 5 |
DOIs | |
State | Published - 2002 |
Externally published | Yes |
Keywords
- Apoptosis
- E2F
- Human p14ARF
- Sp1-like factors
- Tumor suppressor
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology