MyJournals Home  

RSS FeedsNon-canonical ubiquitination of the cholesterol-regulated degron of squalene monooxygenase [Lipids] (Journal of Biological Chemistry)


17 may 2019 10:01:42

Non-canonical ubiquitination of the cholesterol-regulated degron of squalene monooxygenase [Lipids] (Journal of Biological Chemistry)

Squalene monooxygenase (SM) is a rate-limiting enzyme in cholesterol synthesis. The region comprising the first 100 amino acids, termed SM N100, represents the shortest cholesterol-responsive degron and enables SM to sense excess cholesterol in the endoplasmic reticulum (ER) membrane. Cholesterol accelerates the ubiquitination of SM by membrane-associated ring-CH type finger 6 (MARCH6), a key E3 ubiquitin ligase involved in ER-associated degradation. However, the ubiquitination site required for cholesterol regulation of SM N100 is unknown. Here, we used SM N100 fused to GFP as a model degron to recapitulate cholesterol-mediated SM degradation and show that neither SM lysine residues nor the N terminus impart instability. Instead, we discovered four serines (Ser-59, Ser-61, Ser-83, and Ser-87) that are critical for cholesterol-accelerated degradation, with MS analysis confirming Ser-83 as a ubiquitination site. Notably, these two clusters of closely spaced serine residues are located in disordered domains flanking a 12-amino acid-long amphipathic helix (residues Gln-62-Leu-73) that together confer cholesterol responsiveness. In description, our findings reveal the degron architecture of SM N100, introducing the role of non-canonical ubiquitination sites and deepening our molecular understanding of how SM is degraded in response to cholesterol. Digg Facebook Google StumbleUpon Twitter
23 viewsCategory: Biochemistry
Human red and green cone opsins are O-glycosylated at an N-terminal Ser/Thr-rich domain conserved in vertebrates [Molecular Bases of Disease] (Journal of Biological Chemistry)
High-resolution structure of RGS17 suggests a role for Ca2+ in promoting the GTPase-activating protein activity by RZ subfamily members [Protein Structure and Folding] (Journal of Biological Chemistry)
blog comments powered by Disqus
The latest issues of all your favorite science journals on one page


Register | Retrieve



Use these buttons to bookmark us: Digg Facebook Google StumbleUpon Twitter

Valid HTML 4.01 Transitional
Copyright © 2008 - 2019 Indigonet Services B.V.. Contact: Tim Hulsen. Read here our privacy notice.
Other websites of Indigonet Services B.V.: Nieuws Vacatures News Tweets Travel Photos Nachrichten Indigonet Finances Leer Mandarijn