Journal Article

Sp1 and p73 activate <i>PUMA</i> following serum starvation

Lihua Ming, Tsukasa Sakaida, Wen Yue, Anupma Jha, Lin Zhang and Jian Yu

in Carcinogenesis

Volume 29, issue 10, pages 1878-1884
Published in print October 2008 | ISSN: 0143-3334
Published online June 2008 | e-ISSN: 1460-2180 | DOI: https://dx.doi.org/10.1093/carcin/bgn150
Sp1 and p73 activate PUMA following serum starvation

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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 p73β 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 Article.  4818 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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