Tbx2 directly represses the expression of the p21(WAF1) cyclin-dependent kinase inhibitor

Sharon Prince, Suzanne Carreira, Keith W Vance, Amaal Abrahams, Colin R Goding

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

T-box factors play a crucial role in the development of many tissues, and mutations in T-box factor genes have been implicated in multiple human disorders. Some T-box factors have been implicated in cancer; for example, Tbx2 and Tbx3 can suppress replicative senescence, whereas Tbx3 can cooperate with Myc and Ras in cellular transformation. The p21(WAF1) cyclin-dependent kinase inhibitor plays a key role in senescence and in cell cycle arrest after DNA damage. Here, using a combination of in vitro DNA-binding, transfection, and chromatin immunoprecipitation assays, we show that Tbx2 can bind and repress the p21 promoter in vitro and in vivo. Moreover, small interfering RNA-mediated down-regulation of Tbx2 expression results in a robust activation of p21 expression. Taken together, these results implicate Tbx2 as a novel direct regulator of p21 expression and have implications for our understanding of the role of T-box factors in the regulation of senescence and oncogenesis, as well as in development.

Original languageEnglish
Pages (from-to)1669-74
Number of pages6
JournalCancer Research
Volume64
Issue number5
DOIs
Publication statusPublished - 1 Mar 2004

Keywords

  • Animals
  • COS Cells
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Gene Expression Regulation
  • Promoter Regions, Genetic
  • Repressor Proteins
  • T-Box Domain Proteins

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