Wild-type and mutant forms of p53 activate human topoisomerase i: A possible mechanism for gain of function in mutants

A. Albor, S. Kaku, M. Kulesz-Martin

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

p53-interacting proteins from mouse epidermal cells and human myelogenous leukemia cells were isolated by affinity chromatography using glutathione S-transferase (GST)-p53 fusion proteins. One of these proteins was topoisomerase I, whose interaction with p53 was recently reported. A carboxyl-terminal fragment containing the last 92 amino acids of p53 (GST- 299-390) was sufficient for binding to topoisomerase I. Nanomolar concentrations of either GST-p53 or GST-299-390 enhanced the catalytic activity of purified human topoisomerase I. Purified wild-type human p53 and point mutants Ser-239, Ser-245, and His-273 were equivalent in their enhancement of human topoisomerase I activity. Because topoisomerase 1 is thought to promote genetic recombination, competence to enhance topoisomerase I catalytic activity coupled with a deficiency in transcriptional activity may be a mechanism for gain of function in mutant p53 proteins.

Original languageEnglish (US)
Pages (from-to)2091-2094
Number of pages4
JournalCancer Research
Volume58
Issue number10
StatePublished - May 15 1998

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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