Accession Number:

ADA386891

Title:

A Novel Apoptotic Protease Activated in Human Breast Cancer Cells after Poisoning Topoisomerase I

Descriptive Note:

Annual rept. 15 Sep 1999-14 Sep 2000

Corporate Author:

CASE WESTERN RESERVE UNIV CLEVELAND OH

Personal Author(s):

Report Date:

2000-10-01

Pagination or Media Count:

133.0

Abstract:

The goal of this grant is to clone the unknown protease activated by the active anti-breast cancer agent, Beta-lapachone Beta-lap. The research team showed for the first time that Beta-lap requires NQ01 1, a two-electron reduction enzyme elevated in many human breast cancers, for activation. The team then characterized the unknown apoptotic protease activated in human breast cancer cells by Beta-lap, defining endpoints which will be essential for the ultimate isolation of this novel apoptotic protease. The unknown protease a is a non-caspase cytsteine protease b cleaves p53, lamin Beta and PARP atypically in an NQO1-dependent manner at a time co-incident with calpain activation appearance of an 18 kDa active form and its movement into the nucleus by confocal microscopy and c is calcium-dependent, where BAPTA-AM and EDTA blocked cell death caused by Beta-lap. Cloning the unknown protease activated by Beta- lap is ongoing by this research team using standard biochemical methodology and p53 andor PARP cleavage site identification.

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE