Lipid droplet-regulating VLDL assembly factor AUP1

Definition:

Plays a role in the translocation of terminally misfolded proteins from the endoplasmic reticulum lumen to the cytoplasm and their degradation by the proteasome. Plays a role in lipid droplet formation. Induces lipid droplet clustering. Recruits ubiquitin-conjugating enzyme UBE2G2 to lipid droplets which facilitates its interaction with ubiquitin ligases AMFR/gp78 and RNF139/TRC8, leading to sterol-induced ubiquitination of HMGCR and its subsequent proteasomal degradation. Also required for the degradation of INSIG1, SREBF1 and SREBF2. Plays a role in regulating assembly and secretion of very low density lipoprotein particles and stability of apolipoprotein APOB.; (Microbial infection) Following Dengue virus infection, required for induction of lipophagy which facilitates production of virus progeny particles.

References:

[1]. Daniel Lohmann, et al. Monoubiquitination of ancient ubiquitous protein 1 promotes lipid droplet clustering. PLoS One. 2013 Sep 5;8(9):e72453. [Content Brief]

[2]. Britta Mueller, et al. SEL1L nucleates a protein complex required for dislocation of misfolded glycoproteins. Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12325-30. [Content Brief]

[3]. Jingshu Zhang, et al. Flaviviruses Exploit the Lipid Droplet Protein AUP1 to Trigger Lipophagy and Drive Virus Production. Cell Host Microbe. 2018 Jun 13;23(6):819-831.e5. [Content Brief]

[4]. Jing Zhang, et al. AUP1 (Ancient Ubiquitous Protein 1) Is a Key Determinant of Hepatic Very-Low-Density Lipoprotein Assembly and Secretion. Arterioscler Thromb Vasc Biol. 2017 Apr;37(4):633-642. [Content Brief]

[5]. Elizabeth J Klemm, et al. Dual role of ancient ubiquitous protein 1 (AUP1) in lipid droplet accumulation and endoplasmic reticulum (ER) protein quality control. J Biol Chem. 2011 Oct 28;286(43):37602-14. [Content Brief]

[6]. Johanna Spandl, et al. Ancient ubiquitous protein 1 (AUP1) localizes to lipid droplets and binds the E2 ubiquitin conjugase G2 (Ube2g2) via its G2 binding region. J Biol Chem. 2011 Feb 18;286(7):5599-606. [Content Brief]

[7]. Youngah Jo, et al. Ancient ubiquitous protein-1 mediates sterol-induced ubiquitination of 3-hydroxy-3-methylglutaryl CoA reductase in lipid droplet-associated endoplasmic reticulum membranes. Mol Biol Cell. 2013 Feb;24(3):169-83. [Content Brief]

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