Structure and Interactions of a Protein Linked to Apoptosis as Response in Prostate Tumors
Final rept. 1 Oct 1998-31 Mar 2001
ROCHESTER UNIV NY
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Androgen ablation can be used to induce apoptosis of certain cancerous prostate cells. Unfortunately, a fraction of prostate cells are androgen-independent and thus resist treatment, leading to a relapse of disease. Par-4 is a protein found to be upregulated in mammalian prostate cancer cells induced to undergo apoptosis, and its presence in both androgen-dependent and androgen-independent prostate cells could be an avenue for inducing apoptosis of the resistant cells. In order to investigate the structurefunction relationship of Par-4, we have performed CD and NMR studies of the C-terminus of this molecule, a region which is responsible for self-association and association of Par-4 with effector molecules. We have shown that the C-terminus exists in equilibrium between an unstructured monomer and a coiled coil structure, and that reduction in pH and temperature can dramatically shift this equilibrium to favor the coiled coil. The pH requirements for coiled coil formation may be related to the fact that Par-4 has been found to interact with endosome-associated proteins.
- Medicine and Medical Research