Physics ABC Seminar: by Prof. Shengyi (Iris) Sun, Wayne State University
This event is in the past.
Regulation of ER Homeostasis in Health and Disease
Shengyi (Iris) Sun
Center for Molecular Medicine and Genetics
Department of Biochemistry, Microbiology and Immunology, Wayne State University
Accumulation of misfolded proteins in the ER underlies over 70 human diseases, although the underlying mechanism remains unclear. In eukaryotes, approximately 30% of all newly synthesized proteins undergo folding and maturation in the endoplasmic reticulum (ER) to reach a proper configuration. During this process, a significant fraction of nascent proteins may fail to fold properly, due to either an unwanted amino acid mutation or an error in the folding process. These proteins in the ER are recognized as misfolded and subsequently targeted to cytosolic proteasome for degradation by ER quality control system known as the ER-associated degradation (ERAD). ERAD mediates the recognition, retro-translocation, and ubiquitination of misfolded proteins (i.e. substrates) from the ER to cytosol for proteasomal degradation. Sel1L and Hrd1 protein complex represents the most conserved ERAD complex from yeast to humans. Our previous studies showed that Sel1L-Hrd1 ERAD is vital and multifaceted, as it mediates indispensable, homeostatic processes via turnover of specific substrates. However, our understanding of the physiological function and pathological importance of Sel1L-Hrd1 ERAD in metabolism remains limited. The goal of our research program is to gain a comprehensive understanding of the cellular and physiological functions of mammalian SEL1L-HRD1 ERAD, with a focus on inflammatory responses and iron metabolism.