Impaired p53 binding to importin: a novel mechanism of cytoplasmic sequestration identified in oxaliplatin-resistant cells.

ABSTRACT: Previous studies have described one nuclear localization signal (NLSI) in p53 and speculated on two additional sites termed NLSII and NLSIII. Drug-resistant KB cells selected with cisplatin or oxaliplatin were found to have increased p53 levels and in oxaliplatin-selected cells, a larger p53 predominantly in the cytoplasm. In oxaliplatin-selected cells a single nucleotide deletion in the sequence-encoding amino acid 382, part of NLSIII, resulted in a frame shift and a 420 amino acid protein (p53(420)). We investigated explanations for the cytoplasmic sequestration of p53(420) while assessing the role, if any, of NLSII and NLSIII in p53 nuclear import. We found that neither NLSII nor NLSIII are essential for p53 nuclear localization. Furthermore, we confirmed p53(420) is able to tetramerize

SUBMITTER: Komlodi-Pasztor E 

PROVIDER: S-EPMC2867326 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature