Cofactors that Mediate Facilitated Tubulin Folding as Novel Targets for Breast Cancer Chemotherapy
Abstract
Microtubules are essential components of dividing cells as part of the mitotic spindle. The principal protein components of microtubules are the alpha and beta-tubulins, which exist as heterodimers. Disruption of the supply of functional heterodimers therefore offers a potential new route in cancer chemotherapy. This concept is distinct from existing approaches which depend on drugs that interfere with microtubule dynamics. The assembly of the alpha/beta-tubulin heterodimer involves interaction of newly synthesized tubulin polypeptides with several tubulin-specific chaperones. These chaperones function by locking alpha and beta-tubulins together into the assembly-competent heterodimer. Our work is geared toward laying the groundwork for the discovery of reagents that would functionally disrupt the de novo assembly of tubulin heterodimers. Here we report progress in obtaining biochemically workable quantities of several of the tubulin-specific chaperones using various host/vector systems, as well as the results of initial biopanning experiments with a bacterioophage display library.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1998
- Accession Number
- ADA368489
Entities
People
- Nicholas J. Cowan
Organizations
- New York University