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

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

Biochemical and biophysical research communications 2017 Sep 02

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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. Copyright © 2017 Elsevier Inc. All rights reserved.

Citation

Xiao Lu, Lingfeng He, Qian Zhou, Meina Wang, Wen-Jun Shen, Salman Azhar, Feiyan Pan, Zhigang Guo, Zhigang Hu. NHERF1 and NHERF2 regulation of SR-B1 stability via ubiquitination and proteasome degradation. Biochemical and biophysical research communications. 2017 Sep 02;490(4):1168-1175