Abstract:
: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 p73beta 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.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Ming L,Sakaida T,Yue W,Jha A,Zhang L,Yu Jdoi
10.1093/carcin/bgn150subject
Has Abstractpub_date
2008-10-01 00:00:00pages
1878-84issue
10eissn
0143-3334issn
1460-2180pii
bgn150journal_volume
29pub_type
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