Next Article in Journal
Triptolide Decreases Cell Proliferation and Induces Cell Death in Triple Negative MDA-MB-231 Breast Cancer Cells
Previous Article in Journal
Structural and Functional Insights into Human Nuclear Cyclophilins
Article Menu
Issue 4 (December) cover image

Export Article

Open AccessArticle
Biomolecules 2018, 8(4), 162; https://doi.org/10.3390/biom8040162

pH-Induced Folding of the Caspase-Cleaved Par-4 Tumor Suppressor: Evidence of Structure Outside of the Coiled Coil Domain

Department of Chemistry and Biochemistry, Old Dominion University, Norfolk, VA 23529, USA
*
Author to whom correspondence should be addressed.
Received: 10 October 2018 / Revised: 20 November 2018 / Accepted: 22 November 2018 / Published: 4 December 2018
Full-Text   |   PDF [1552 KB, uploaded 13 December 2018]   |  

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. View Full-Text
Keywords: prostate apoptosis response-4 (Par-4); intrinsically disordered protein (IDP); cancer; circular dichroism; coiled coil (CC), leucine zipper (LZ), apoptosis prostate apoptosis response-4 (Par-4); intrinsically disordered protein (IDP); cancer; circular dichroism; coiled coil (CC), leucine zipper (LZ), apoptosis
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Clark, A.M.; Ponniah, K.; Warden, M.S.; Raitt, E.M.; Yawn, A.C.; Pascal, S.M. pH-Induced Folding of the Caspase-Cleaved Par-4 Tumor Suppressor: Evidence of Structure Outside of the Coiled Coil Domain. Biomolecules 2018, 8, 162.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Biomolecules EISSN 2218-273X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top