Repression of Transcription and Interference with DNA Binding of TATA-Binding Protein by C-Terminal Alternatively Spliced p53

• Published in: Experimental cell research Vol. 279; no. 2; pp. 248 - 259
• Main Authors: Huang, Hua, Kaku, Shinsuke, Knights, Chad D., Park, Byung S., Clifford, Jane, Kulesz-Martin, Molly
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2002
• Subjects: Alternative Splicing; Animals; Cell Line; Cyclin-Dependent Kinase Inhibitor p21; Cyclins - genetics; Cyclins - metabolism; DNA - metabolism; DNA-Binding Proteins - metabolism; Enzyme Inhibitors - metabolism; Gene Expression Regulation; Genes, Reporter; Mice; p53; Promoter Regions, Genetic; TATA Box; TATA-binding protein; TATA-Box Binding Protein; transactivation; Transcription Factors - metabolism; Transcription, Genetic; transcriptional repression; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Waf-1; TATA-binding protein; transcriptional repression; Waf-1; p53; transactivation
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1006/excr.2002.5596

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 p21 WAF1/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.