Document Type

Article

Publication Date

12-2018

DOI

10.3390/biom8040162

Publication Title

Biomolecules

Volume

8

Issue

4

Pages

162 (17 pages)

Abstract

Prostate apoptosis response-4 (Par-4) is a 38 kDa largely intrinsically disordered tumor suppressor protein that functions in cancer cell apoptosis. Par-4 down-regulation is often observed in cancer while up-regulation is characteristic of neurodegenerative conditions such as Alzheimer’s disease. Cleavage of Par-4 by caspase-3 activates tumor suppression via formation of an approximately 25 kDa fragment (cl-Par-4) that enters the nucleus and inhibits Bcl-2 and NF-ƙB, which function in pro-survival pathways. Here, we have investigated the structure of cl-Par-4 using biophysical techniques including circular dichroism (CD) spectroscopy, dynamic light scattering (DLS), and intrinsic tyrosine fluorescence. The results demonstrate pH-dependent folding of cl-Par-4, with high disorder and aggregation at neutral pH, but a largely folded, non-aggregated conformation at acidic pH

Comments

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.

Original Publication Citation

Clark, A. M., Ponniah, K., Warden, M. S., Raitt, E. M., Yawn, A. C., & Pascal, S. M. (2018). pH-induced folding of the caspase-cleaved par-4 tumor suppressor: Evidence of structure outside of the coiled coil domain. Biomolecules, 8(4), 182. doi:10.3390/biom8040162

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