Journal
CARCINOGENESIS
Volume 29, Issue 10, Pages 1878-1884Publisher
OXFORD UNIV PRESS
DOI: 10.1093/carcin/bgn150
Keywords
-
Categories
Funding
- Flight Attendant Medical Research Institute
- Alliance for Cancer Gene Therapy
- University of Pittsburgh Cancer Institute [1 P50 CA097190]
- National Institutes of Heath [CA106348, CA121105]
- American Cancer Society [RSG-07-156-01-CNE]
Ask authors/readers for more resources
p53-upregulated modulator of apoptosis (PUMA) plays an essential role in p53-dependent apoptosis following DNA damage. PUMA also mediates apoptosis independent of p53. In this study, we investigated the role and mechanism of PUMA induction in response to serum starvation in p53-deficient cancer cells. Following serum starvation, the binding of Sp1 to the PUMA promoter significantly increased, whereas inhibition of Sp1 completely abrogated PUMA induction. p73 was found to be upregulated by serum starvation and mediate PUMA induction through the p53-binding sites in the PUMA promoter. Sp1 and p73 beta appeared to cooperatively activate PUMA transcription, which is inhibited by the phosphoinsitide 3-kinase (PI3K)-protein kinase B (AKT) pathway. Furthermore, knockdown of PUMA suppressed serum starvation-induced apoptosis in leukemia cells. Our results suggest that transcription factors Sp1 and p73 mediate p53-independent induction of PUMA following serum starvation to trigger apoptosis in human cancer cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available