Activation of the cryptic DNA binding function of mutant forms of p53
Year: 1993
Type: article
Abstract: Wild type p53 assembles into a latent multiprotein complex which can be activated for sequence-specific DNA binding in vitro by proteins targeting the carboxy-terminal domain. Using an optimized system coupling the post-translational modification of wild type p53 to activation of sequence specific DNA binding, we examined the affects of common mutations on the cryptic DNA binding function of p53. Two mutant forms of p53 were shown to be efficiently converted from the latent state by PAb421 and DnaK, but were defective in activation by casein kinase II, indicating that mutant p53 may not be receptive to allosteric regulation by casein kinase II phosphorylation. A reactive sulfhydryl group is absolutely required for DNA binding by wild type and mutant forms of p53 once converted to the activated state. Together, these data show that some mutant forms of p53 harbour the wild-type machinery required to engage in sequence-specific DNA binding and define a signalling pathway whose inactivation may directly result in a loss of p53 function.
Source: Nucleic Acids Research
Institution: MRC Protein Phosphorylation and Ubiquitylation Unit
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: Pfizer
OpenAlex ID: W2005546492