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

Hua Huang1, Shinsuke Kaku, Chad Knights

  • 1Department of Experimental Therapuetics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.

Experimental Cell Research
|September 24, 2002
PubMed

Insights

A naturally occurring mouse p53 variant (p53as) binds DNA more efficiently and represses transcription better than the regular p53 protein (p53r). This p53 variant shows enhanced interference with transcription factor binding, highlighting its novel role in gene regulation.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • The p53 protein (p53r) is a critical tumor suppressor.
  • A C-terminal alternatively spliced variant, p53-associated (p53as), occurs naturally in mouse cells.
  • Previous studies suggest p53as binds DNA more efficiently than p53r.

Purpose of the Study:

  • To investigate the functional differences between p53as and p53r.
  • To elucidate the role of p53as in transcriptional regulation, including repression.
  • To examine the interaction of p53as with TATA-binding protein (TBP).

Main Methods:

  • Ectopic expression of p53as and p53r in p53-deficient cells.
  • Reporter plasmid assays to assess transactivation and repression.
  • Analysis of protein-protein interactions with TBP.
  • DNA binding assays to evaluate interference with TBP binding.

Main Results:

  • Both p53as and p53r transactivated reporter plasmids with p53 binding sites.
  • p53as demonstrated superior efficiency in transcriptional repression of promoters lacking p53 binding sites.
  • p53as exhibited concentration-dependent repression of the p21(WAF1/Cip-l/Sdi) promoter.
  • p53as associated with TBP, similar to p53r, but interfered more effectively with TBP's DNA binding.

Conclusions:

  • The naturally occurring p53as protein plays a significant role in transcriptional repression.
  • Differences in DNA binding properties contribute to p53as's enhanced repression activity.
  • p53as represents a novel functional variant of p53 with distinct regulatory capabilities, potentially impacting gene expression and cellular processes.

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