PT  - JOURNAL ARTICLE
AU  - Albor, Amador
AU  - Kaku, Shinsuke
AU  - Kulesz-Martin, Molly
TI  - Wild-Type and Mutant Forms of p53 Activate Human Topoisomerase I: A Possible Mechanism for Gain of Function in Mutants
DP  - 1998 May 15
TA  - Cancer Research
PG  - 2091--2094
VI  - 58
IP  - 10
4099  - http://cancerres.aacrjournals.org/content/58/10/2091.short
4100  - http://cancerres.aacrjournals.org/content/58/10/2091.full
SO  - Cancer Res1998 May 15; 58
AB  - 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 I 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. ©1998 American Association for Cancer Research.