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.
- 1. Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China.
- 2. Geriatric Research, Education and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA; Division of Endocrinology, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
- 3. Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China. Electronic address: [email protected].
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.