Reactome | MYLIP dimer ubiquitinates VLDLR on Lys-839

MYLIP dimer ubiquitinates VLDLR on Lys-839

Stable Identifier

R-HSA-8854628

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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MYLIP dimer ubiquitinates VLDLR on Lys-839

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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