Runnebohm AM, Evans MD, Richardson AE, Turk SM, Olesen JB, Smaldino PJ, Rubenstein EM. microPublication Biology, published online ( ), 2020. Endoplasmic reticulum stress-regulated degradation of a translocon-associated protein is independent of integrated stress response transcription factor Gcn4p. Glucose concentration does not affect degradation of a protein that aberrantly engages the endoplasmic reticulum translocon. Publicationsīroshar CL, Rubenstein EM (2020). Such an improved understanding may inform the development of improved therapeutic strategies for cholesterol-related (and potentially other) pathologies.įollow the Rubenstein Lab on Twitter or visit our website. A long-term goal of our laboratory is to understand the mechanism of ERAD-T using budding yeast (Saccharomyces cerevisiae) as a model organism. “bad cholesterol”) is also targeted for degradation by Hrd1 when its translocation into the ER has stalled (e.g. Mammalian apolipoprotein B (a component of low-density lipoproteins, LDL, i.e. ERAD-T is mediated by the Hrd1 ubiquitin ligase but differs fundamentally from other characterized Hrd1-dependent ERAD pathways. We have identified one such mechanism for the destruction of proteins that persistently or aberrantly engage the ER translocon, termed ERAD-T (ER-Associated Degradation of Translocon-clogging proteins).
In this way, the clogged translocon may resume its function in transporting other proteins across the ER membrane.
Cells employ multiple protein quality control mechanisms to recognize and destroy translocon-clogging proteins. For poorly characterized reasons, endomembrane system and secretory proteins may stall in the ER translocon (the primary channel responsible for moving proteins across the ER membrane). Misfolded and potentially harmful proteins that accumulate at the endoplasmic reticulum (ER) are degraded via one of several forms of protein quality control. The loss of regulated protein degradation is involved in the pathogenesis of many human diseases, including cancer, neurodegenerative conditions, cystic fibrosis, and cholesterol-related pathologies. Grove City College, BS (1998 - 2002) Research Interests University of Pittsburgh School of Medicine, PhD (2003 - 2008)
Yale University, Postdoctoral Fellowship (2008 - 2012)
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