p150Sal2 Is a p53-Independent Regulator of p21WAF1/CIP

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American Society for Microbiology

RESUMO

p150Sal2, a vertebrate homologue of the Drosophila melanogaster homeotic transcription factor Spalt, has previously been shown to be a binding target of the polyomavirus large T antigen. p150Sal2 acts as an inhibitor of viral DNA synthesis, and the binding of p150Sal2 by large T overcomes this inhibition. The present study focuses on the effects of p150Sal2 on the growth and survival of ovarian carcinoma (OVCA) cells that are deficient in expression of p150Sal2 and of normal established human ovarian surface epithelial (HOSE) cells which abundantly express the protein. Transient expression of exogenous p150Sal2 in OVCA cells that show little or no endogenous expression resulted in inhibition of DNA synthesis and colony formation and in increased apoptosis. OVCA cells stably transfected and expressing physiological levels of p150Sal2 showed reduced tumorigenicity accompanied by increased expression of p21WAF1/CIP1 (p21) and BAX. Conversely, reduction of endogenous levels of p150Sal2 in HOSE resulted in reduced p21 expression and increased DNA synthesis. p150Sal2 bound to the p21 promoter adjacent to the known p53 binding sites and stimulated transcription in the absence of p53. We propose that p150Sal2, acting in part as a p53-independent regulator of p21 and BAX, can function in some cell types as a regulator of cell growth and survival.

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