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The regulation of protein degradation at the endoplasmic reticulum
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Date
2021-06-28
Authors
O'Nualláin, Fearghal
Journal Title
Journal ISSN
Volume Title
Publisher
University College Cork
Published Version
Abstract
The majority of membrane and secretory protein synthesis in the cell occurs in the endoplasmic reticulum (ER) where proteins reach their native energy stable folded state and are subsequently transported to their functional location. Aberrations in this process whereby a protein cannot reach its intended location or cannot fold correctly often result in accumulation of that protein in the ER lumen. This is toxic to the cell and ER stress is induced in an effort to remove the misbehaving protein to avoid cellular stress and damage. Chaperones can be recruited to assist protein folding but if this is unsuccessful then the protein is marked for degradation via endoplasmic reticulum associated degradation (ERAD). Ubc6 (UBE2J2 in humans) is an E2 ubiquitin conjugating enzyme which catalyses the attachment of ubiquitin to target proteins which marks them for degradation. However, the specific set of substrates which Ubc6 acts upon and the mechanism for its regulation is
yet to be understood. In this study, we construct a protein-protein interaction network (PPIN) of Ubc6 to better understand where this protein fits into its environment and to help elucidate what substrates it mediates degradation for. Here, we demonstrate how Ubc6 has the ability to mediate degradation for both a plasma membrane resident protein E-cadherin and also an ER trapped protein HFE C282 (HFE-M). We also show the increased expression of Ubc6 by MAPK signalling through phorbol-12-myristate 13-acetate (PMA) incubation and constitutive BRaf signalling (V600E). Whether this increased expression results in higher Ubc6 stability and/or increased substrate degradation remains to be seen.
Description
Keywords
ERAD , Ubc6 , BRAF V600E , UBE2J2 , Ubiquitin , E-cadherin , HFE C282Y , Protein degradation
Citation
O'Nualláin, F. 2021. The regulation of protein degradation at the endoplasmic reticulum. MSc Thesis, University College Cork.