MYLIP dimer ubiquitinates VLDLR on Lys-839

Stable Identifier
Reaction [transition]
Homo sapiens
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The E3 ubiquitin-protein ligase (MYLIP, aka IDOL) mediates the lysine-63 polyubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8 (Sorrentino et al. 2011). It acts as a sterol-dependent inhibitor of cellular cholesterol uptake by mediating degradation of LDLR (Hong et al. 2010). Despite some similarities, the MYLIP and PCSK9 ubiquitination pathways for controlling (V)LDLR abundance appear to be independent of each other. MYLIP is a transcriptional target of liver X receptors (NR1H2 and NR1H3), which can increase MYLIP expression and hence decerease (V)LDLR levels (Zelcer et al. 2009, Hong et al. 2010, Sorrentino & Zelcer 2010, Zhang et al. 2012).

Literature References
PubMed ID Title Journal Year
21734303 Distinct functional domains contribute to degradation of the low density lipoprotein receptor (LDLR) by the E3 ubiquitin ligase inducible Degrader of the LDLR (IDOL)

Bleijlevens, B, Reits, E, Scheer, L, Zelcer, N, Sorrentino, V, Santos, A

J Biol Chem 2011
22510808 Post-transcriptional regulation of lipoprotein receptors by the E3-ubiquitin ligase inducible degrader of the low-density lipoprotein receptor

Zelcer, N, Sorrentino, V

Curr. Opin. Lipidol. 2012
19520913 LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor

Zelcer, N, Hong, C, Tontonoz, P, Boyadjian, R

Science 2009
22936343 Feedback regulation of cholesterol uptake by the LXR-IDOL-LDLR axis

Zhang, L, Reue, K, Fong, LG, Tontonoz, P, Young, SG

Arterioscler. Thromb. Vasc. Biol. 2012
20427281 The E3 ubiquitin ligase IDOL induces the degradation of the low density lipoprotein receptor family members VLDLR and ApoER2

Lindholm, D, van Berkel, TJ, Nimpf, J, Duit, S, Foley, E, Scheer, L, Korhonen, L, Zelcer, N, Sorrentino, V, Rodenburg, KW, Out, R, Tontonoz, P, Boyadjian, R, Jalonen, P, Hong, C

J. Biol. Chem. 2010
Catalyst Activity

ubiquitin protein ligase activity of MYLIP dimer [cytosol]

This event is regulated
Orthologous Events
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