Description:

The Department of Microbiology-Immunology Seminar Series

"From Bacterial Pathogenesis to Stress Response: Fic Proteins in Cell Signaling"

Seema Mattoo, PhD -  Purdue University

Description

Fic proteins are a newly discovered family of enzymes that carry out diverse post-translational modifications (PTMs), predominantly adenylylation/AMPylation – i.e., the covalent attachment of AMP (adenosine monophosphate) to the target protein. Pathogenic bacteria have been shown to secrete Fic proteins to AMPylate and inactivate mammalian Rho GTPases, thereby inducing cytotoxicity. Fic-mediated adenylylation is conserved across evolution. Dr. Mattoo’s group discovered that the human Fic protein, HYPE, AMPylates the Hsp70 chaperone, BiP, in the lumen of the endoplasmic reticulum (ER). In so doing, HYPE alters how eukaryotic cells respond to ER stress via a pathway called the unfolded protein response (UPR). Thus, HYPE was discovered as a novel regulator of ER homeostasis and a critical determinant of cell fate. PTMs mediated by Fic proteins are now recognized as a universal signaling paradigm that regulate critical cellular processes like bacterial pathogenesis, cell division, stress survival, and cellular trafficking. Dr. Mattoo will describe studies from her laboratory that have contributed to understanding the diverse signaling events mediated by Fic proteins.