162 (17 pages)
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
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
Clark, Andrea M.; Ponniah, Komala; Warden, Meghan S.; Raitt, Emily M.; Yawn, Andrea C.; and Pascal, Stephen M., "pH-Induced Folding of the Caspase-Cleaved Par-4 Tumor Suppressor: Evidence of Structure Outside of the Coiled Coil Domain" (2018). Chemistry & Biochemistry Faculty Publications. 160.