A Novel Apoptotic Protease Activated in Human Breast Cancer Cells After Poisoning Topoisomerase I
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, 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 B, and PARP (atypically) in an NQ01-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 (e.g., the proteolytic cleavage of PARP or p53 was blocked by co-administration of EGTA or EDTA), and the drug causes massive NQ01-dependent calcium influx within 3 mins posttreatment with 5-8 micro B-lap.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADB260285
Entities
People
- David Boothman
Organizations
- Case Western Reserve University