Faculty Candidate Seminar: Andrew Truman, Postdoctoral Scholar, Kron Lab, University of Chicago

Event Date: March 07, 2014 - 10 a.m.
Event Type: Open to public
Location: Science Center, Chemistry Conference Room (Science S01-0089)

University of Massachusetts Boston

Department of Chemistry

Faculty Candidate Seminar

Dealing with Difficult Clients: Modulating Hsp70 Function As a Novel Anti-Cancer Strategy

Dr. Andrew Truman

Postdoctoral Scholar

Kron Laboratory

Department of Molecular Genetics and Cell Biology, University of Chicago

Chicago, IL

Friday, March 7, 2014 | 11:00 AM

Chemistry Conference Room (Science S01-0089)

Hsp70 is a universally conserved molecular chaperone that performs a wide variety of functions in the cell, including folding of both newly synthesized and denatured protein "clients", protein transport and disaggregation of oligomerized proteins. Although transcriptional regulation of Hsp70 has been highly studied, little is known about post-translational modifications on Hsp70 and their effects on in vivo function. Using the model organism Saccharomyces Cerevisiae (budding yeast), we show that phosphorylation of yeast Hsp70 (Ssa1) on Threonine 36 alters co-chaperone and global client interactions. Threonine 36 phosphorylation triggers displacement of the co-chaperone Ydj1, allowing Ssa1 to bind the G1 cyclin Cln3 and promote its degradation.

In mammalian cells, Cyclin D1 (homologue of Cln3) forms a complex with CDK4 to phosphorylate important cell cycle proteins such as Rb to drive G1/S progression. As such, down regulation of Cyclin D1 function may offer a way to curb uncontrolled cell cycle progression seen in many cancers. We find that CDK-dependent phosphorylation of Hsp70 on Threonine 38 similarly regulates Cyclin D1 binding, stability and Cyclin D1-mediated signaling. These findings offer the possibility of a novel anti-cancer strategy, whereby inhibition of Cyclin D1 may be achieved by manipulating Hsp70 phosphorylation status.

For disability-related accommodations, including dietary accommodations, please visit www.ada.umb.edu two weeks prior to the event.