A movable and regulable inactivation function within the central region of a temperature-sensitive p53 mutant.
p53 is the most frequently mutated gene in human cancer. Naturally occurring mutations of p53 are mainly located within a region containing residues 100-300 and are predominantly of missense type, resulting in loss of the protein's DNA binding activity. Here we show that this type of mutation also represses the p53 N-terminal activation domain. The repression activity is localized in the central region of mutant p53 containing residues 101-318. Interestingly, the central region of a temperature-sensitive mutant p53N247I possesses a movable and regulable inactivation function. It represses other activities present on the same polypeptide chain without strict regard to the configuration of that polypeptide only at the nonpermissive temperature (37 degrees C) and not at the permissive temperature (30 degrees C). Furthermore, this mutant p53 region exhibits no other activity, and its function is independent of endogenous p53 status.
Chuang
J Y
JY
Institute of Biomedical Sciences, Academia Sinica, Taipei, Tiawan.
Lin
C T
CT
Wu
C W
CW
Lin
Y S
YS
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016466:CHO Cells; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D006224:Cricetinae; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000096:biosynthesis; D016158:Genes, p53; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D015183:Restriction Mapping; D029701:Saccharomyces cerevisiae Proteins; D013696:Temperature; D014157:Transcription Factors; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D009838:Oligodeoxyribonucleotides; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D015500:Chloramphenicol O-Acetyltransferase