2. Academic Validation
  3. NHERF1 and NHERF2 regulation of SR-B1 stability via ubiquitination and proteasome degradation

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.
Xiao Lu 1,  Lingfeng He 1,  Qian Zhou 1,  Meina Wang 1,  Wen-Jun Shen 2,  Salman Azhar 2,  Feiyan Pan 1,  Zhigang Guo 1,  Zhigang Hu 3
Affiliations

Affiliations

  • 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: huzg_2000@126.com.
PMID: 28669731 DOI: 10.1016/j.bbrc.2017.06.175
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.

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