College

College of Sciences

Department

Chemistry and Biochemistry

Program

Chemistry

Publication Date

4-2021

Abstract

Prostate apoptosis response-4 (Par-4) is a pro-apoptotic tumor suppressor protein. We have shown that this 38 kDa full-length Par-4 (Fl-Par-4) protein is predominantly intrinsically disordered in vitro. In vivo, Par-4 is cleaved by caspase-3 at Asp-131 to generate a 24 kDa functionally active cleaved Par-4 (cl-Par-4) fragment. The cl-Par-4 protein inhibits the NF-κB-mediated cell survival pathway and causes selective apoptosis in various tumor cells. Our laboratory is interested in how the disorder-order balance within Fl-Par-4 and cl-Par-4 may be related to the balance between cell survival and cell death. Currently, we are using biophysical techniques such as circular dichroism (CD) spectroscopy, dynamic light scattering (DLS), UV-vis spectroscopy and SDS-PAGE to characterize the structure of cl-Par-4 in the presence of various concentrations of monovalent and divalent ions, in order to shed light on the possible ion-specific role of cl-Par-4 in inducing structure and self-association of this protein. Results show that effects on cl-Par-4 conformation are ion-specific, and effects of divalent cations are considerably more pronounced than effects from monovalent cations. We have also found that the anion moiety of a salt possesses almost negligible influence.

Keywords

Intrinsically disordered protein (IDP), Prostate apoptosis response-4 (Par-4), Tumor suppressor, Circular dichroism (CD) spectroscopy, Dynamic light scattering (DLS)

Disciplines

Biochemistry | Cancer Biology | Cell Biology | Chemistry

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Influence of Monovalent and Divalent Ions in the Conformational Change of Caspase-Cleaved Par-4 (cl-Par-4) Tumor Suppressor Protein


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