Snail regulates p21(WAF/CIP1) expression in cooperation with E2A and Twist.

Document Type

Article

Publication Date

2004

Keywords

Cell-Differentiation, Cell-Line, Cells-Cultured, DNA-Binding-Proteins, Fibroblasts, Gene-Expression-Regulation, Humans, Nuclear-Proteins, Osteoblasts, Recombinant-Proteins, Repressor-Proteins, Transcription-Factors

First Page

1136

Last Page

1144

JAX Source

Biochem Biophys Res Commun 2004 Dec; 325(4):1136-44.

Abstract

Snail, a zinc-finger transcriptional repressor, is essential for mesoderm and neural crest cell formation and epithelial-mesenchymal transition. The basic helix-loop-helix transcription factors E2A and Twist have been linked with Snail during embryonic development. In this study, we examined the role of Snail in cellular differentiation through regulation of p21(WAF/CIP1) expression. A reporter assay with the p21 promoter demonstrated that Snail inhibited expression of p21 induced by E2A. Co-expression of Snail with Twist showed additive inhibitory effects. Deletion mutants of the p21 promoter revealed that sequences between -270 and -264, which formed a complex with unidentified nuclear factor(s), were critical for E2A and Snail function. The E2A-dependent expression of the endogenous p21 gene was also inhibited by Snail.

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