Structure and Interactions of a Protein Linked to Apoptosis Response in Prostate Tumors
Abstract
Par-4 (prostate apoptosis response protein #4) was first identified as a protein preferentially expressed in rat prostate tissue upon induction of apoptosis. Its effect on expressing cells is to infer super-sensitivity to apoptotic stimuli. Par-4 induction is an early and pivotal response in the apoptotic pathway, and its mode of action has been traced to interaction with zinc-binding domains of three proteins: the atypical PKC isoforms zeta and lambda/iota, and WT1. The interaction between the Par-4 C-terminal region (CTR) and the atypical PKCs has been shown to repress the kinase activity, leading to enhanced cell death. We have succeeded in creating multiple expression plasmids coding for the Par-4 CTR and the PKC-zeta and PKC-lambda/iota Zn-binding domains, and have purified the corresponding polypeptides from E. coli hosts. CD spectra and preliminary NMR spectra indicate that the Par-4 CTR is highly helical and self-associating, consistent with its predicted Leucine Zipper structure. Interactions with a native-like fold of the PKC-zeta peptide have been preliminarily confirmed, and studies are underway to prepare for determination of the interaction interface and the structure of the complex to atomic resolution.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADB258856
Entities
People
- Steven M. Pascal
Organizations
- University of Rochester