Tumor suppressor p53 gene forms multiple isoforms: evidence for single locus origin and cytoplasmic complex formation with heat shock proteins.
The tumor suppressor protein p53 is a major cell cycle control factor, and mutations in p53 are the most common genetic lesion found in human tumors, resulting in loss of function and contributing to malignant transformation. This report reviews several studies which show that p53 protein appears as at least eleven isoforms having the same amino acid backbone but varying in charge by level of phosphorylation. All isoforms are derived from a single locus, which indicates that p53 activity is modulated by post-translational modification. In addition, mutant p53 forms hetero-oligomers with two families of proteins: HSP70 and a 90 kDa group similar to HSP90. Cytoplasmic complexes are most likely formed to protect p53 from proteolysis and are probably involved in translocation of activated p53 from the cytoplasm to the nucleus for transactivation of other cell cycle control genes.
Selkirk
J K
JK
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
He
C
C
Patterson
R M
RM
Merrick
B A
BA
D000818:Animals; D001692:Biological Transport; D001943:Breast Neoplasms / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D016158:Genes, p53; D018841:HSP90 Heat-Shock Proteins / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D010996:Pleural Effusion / Q000473:pathology; D017354:Point Mutation; D011499:Protein Processing, Post-Translational; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000302:isolation & purification / Q000378:metabolism*
D018841:HSP90 Heat-Shock Proteins; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D016159:Tumor Suppressor Protein p53