p150(Sal2) is a p53-independent regulator of p21(WAF1/CIP).
p150(Sal2), 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. p150(Sal2) acts as an inhibitor of viral DNA synthesis, and the binding of p150(Sal2) by large T overcomes this inhibition. The present study focuses on the effects of p150(Sal2) on the growth and survival of ovarian carcinoma (OVCA) cells that are deficient in expression of p150(Sal2) and of normal established human ovarian surface epithelial (HOSE) cells which abundantly express the protein. Transient expression of exogenous p150(Sal2) 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 p150(Sal2) showed reduced tumorigenicity accompanied by increased expression of p21(WAF1/CIP1) (p21) and BAX. Conversely, reduction of endogenous levels of p150(Sal2) in HOSE resulted in reduced p21 expression and increased DNA synthesis. p150(Sal2) bound to the p21 promoter adjacent to the known p53 binding sites and stimulated transcription in the absence of p53. We propose that p150(Sal2), 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.
Li
Dawei
D
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Tian
Yu
Y
Ma
Yupo
Y
Benjamin
Thomas
T
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D010051:Ovarian Neoplasms / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C494827:Bax protein, mouse; C493956:CDKN1A protein, human; D002352:Carrier Proteins; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C403266:Sall2 protein, mouse; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein