Repression of transcription and interference with DNA binding of TATA-binding protein by C-terminal alternatively spliced p53

Hua Huang, Shinsuke Kaku, Chad D. Knights, Byung S. Park, Jane Clifford, Molly Kulesz-Martin

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

The protein encoded by C-terminal alternatively spliced p53 mRNA (p53as) has been shown previously to occur naturally in mouse cells and to bind sequence-specifically to DNA more efficiently than p53 (p53r, regular form). In the current study, p53as and p53r proteins ectopically expressed in p53-deficient cells each transactivated reporter plasmids containing p53 binding sites. However, p53as consistently was more efficient in transcriptional repression of promoters lacking p53 binding sites and in concentration-dependent repression of the p21WAF1/Cip-l/Sdi promoter sequence. The p53as protein, like p53r, associated with TATA-binding protein (TBP), indicating that this interaction does not require the last 26 amino acids of p53. Consistent with its stronger repression effects, p53as interfered with TBP binding to a TATA-containing DNA sequence more efficiently than p53r protein. Taken together, these in vitro and in vivo results demonstrate a novel role in transcriptional repression for a naturally occurring C-terminal variant form of mouse p53 protein associated with differences in DNA binding properties and interference with transcription factor binding.

Original languageEnglish (US)
Pages (from-to)248-259
Number of pages12
JournalExperimental Cell Research
Volume279
Issue number2
DOIs
StatePublished - Jan 1 2002

Keywords

  • TATA-binding protein
  • Transactivation
  • Transcriptional repression
  • Waf-1
  • p53

ASJC Scopus subject areas

  • Cell Biology

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