NHERF1 and NHERF2 regulation of SR-B1 stability via ubiquitination and proteasome degradation

Biochem Biophys Res Commun. 2017 Sep 2;490(4):1168-1175. doi: 10.1016/j.bbrc.2017.06.175. Epub 2017 Jun 29.

Abstract

Scavenger receptor class B type 1 (SR-B1), an HDL receptor plays a crucial role in cholesterol metabolism in the liver, steroidogenic tissues, and vascular cells including macrophages. SR-B1 is subject to regulation at the transcription, posttranscription and posttranslational levels. We previously provided evidence that PDZ domain containing NHERF1 and NHERF2 regulate SR-B1 protein levels post-transcriptionally, although the underlying mechanism(s) by which NHERF1 and NHERF2 regulate SR-B1 protein levels is not well understood. In this study, we demonstrate that SR-B1 is degraded intracellularly via ubiquitin-proteasome pathway and that SR-B1 can be ubiquitinated at K500 and K508 residues. Overexpression of NHERF1 or NHERF2 enhanced SR-B1 ubiquitination and degradation. NHERF1 and NHERF2 promote SR-B1 ubiquitination at sites K508 and K500, respectively. These results suggest that NHERF1 and NHERF2 down-regulated SR-B1 at least in part via the ubiquitin/proteasome pathway.

Keywords: NHERF1; NHERF2; Protein stability; SR-B1; Ubiquitination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cells, Cultured
  • Cricetulus
  • Phosphoproteins / metabolism*
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Stability
  • Rats
  • Scavenger Receptors, Class B / metabolism*
  • Sodium-Hydrogen Exchangers / metabolism*
  • Ubiquitination

Substances

  • Phosphoproteins
  • Scarb1 protein, rat
  • Scavenger Receptors, Class B
  • Slc9a3r2 protein, rat
  • Sodium-Hydrogen Exchangers
  • sodium-hydrogen exchanger regulatory factor
  • Proteasome Endopeptidase Complex