TY - JOUR
T1 - Repression of transcription and interference with DNA binding of TATA-binding protein by C-terminal alternatively spliced p53
AU - Huang, Hua
AU - Kaku, Shinsuke
AU - Knights, Chad D.
AU - Park, Byung S.
AU - Clifford, Jane
AU - Kulesz-Martin, Molly
N1 - Funding Information:
We are grateful to Laura Lee and Barbara Lisafeld for technical assistance and Jennifer Carlson and Michelle Bryant for help with the preparation of this manuscript. This work was supported by NCI CA31101, RPCI Core Grant CA16056, a research grant from Taisho Pharmaceutical Co., Ltd., Tokyo, Japan, OHSU Cancer Institute CA69533, and a Tartar Trust Fellowship of OHSU to C. D. Knights.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - TATA-binding protein
KW - Transactivation
KW - Transcriptional repression
KW - Waf-1
KW - p53
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U2 - 10.1006/excr.2002.5596
DO - 10.1006/excr.2002.5596
M3 - Article
C2 - 12243750
AN - SCOPUS:0036405612
SN - 0014-4827
VL - 279
SP - 248
EP - 259
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 2
ER -