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).
Bleijlevens, B, Reits, E, Scheer, L, Zelcer, N, Sorrentino, V, Santos, A
Zelcer, N, Sorrentino, V
Zelcer, N, Hong, C, Tontonoz, P, Boyadjian, R
Zhang, L, Reue, K, Fong, LG, Tontonoz, P, Young, SG
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
ubiquitin protein ligase activity of MYLIP dimer [cytosol]
© 2023 Reactome
