O-GlcNAc regulates NEDD4-1 stability via caspase-mediated pathway

Kuan Jiang; Bingyang Bai; Yajie Ta; Tingling Zhang; Zikang Xiao; Peng George Wang; Lianwen Zhang

doi:10.1016/j.bbrc.2016.02.037

O-GlcNAc regulates NEDD4-1 stability via caspase-mediated pathway

Biochem Biophys Res Commun. 2016 Mar 18;471(4):539-44. doi: 10.1016/j.bbrc.2016.02.037. Epub 2016 Feb 12.

Authors

Kuan Jiang¹, Bingyang Bai¹, Yajie Ta¹, Tingling Zhang¹, Zikang Xiao¹, Peng George Wang², Lianwen Zhang³

Affiliations

¹ State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Collaborative Innovation Center for Biotherapy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300071, China.
² State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Collaborative Innovation Center for Biotherapy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300071, China. Electronic address: pwang@nankai.edu.cn.
³ State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Collaborative Innovation Center for Biotherapy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300071, China. Electronic address: lianwen@nankai.edu.cn.

PMID: 26876577
DOI: 10.1016/j.bbrc.2016.02.037

Abstract

O-GlcNAc modification of cytosolic and nuclear proteins regulates essential cellular processes such as stress responses, transcription, translation, and protein degradation. Emerging evidence indicates O-GlcNAcylation has a dynamic interplay with ubiquitination in cellular regulation. Here, we report that O-GlcNAc indirectly targets a vital E3 ubiquitin ligase enzyme of NEDD4-1. The protein level of NEDD4-1 is accordingly decreased following an increase of overall O-GlcNAc level upon PUGNAc or glucosamine stimulation. O-GlcNAc transferase (OGT) knockdown, overexpression and mutation results confirm that the stability of NEDD4-1 is negatively regulated by cellular O-GlcNAc. Moreover, the NEDD4-1 degradation induced by PUGNAc or GlcN is significantly inhibited by the caspase inhibitor. Our study reveals a regulation mechanism of NEDD4-1 stability by O-GlcNAcylation.

Keywords: Caspase; NEDD4-1; O-GlcNAcylation; OGT.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylglucosamine / analogs & derivatives*
Acetylglucosamine / genetics
Acetylglucosamine / metabolism
Acylation
Caspases / metabolism*
Endosomal Sorting Complexes Required for Transport / chemistry
Endosomal Sorting Complexes Required for Transport / metabolism*
Enzyme Stability
Gene Knockout Techniques
HEK293 Cells
Humans
MCF-7 Cells
Metabolic Networks and Pathways
Mutation
N-Acetylglucosaminyltransferases / genetics
N-Acetylglucosaminyltransferases / metabolism
Nedd4 Ubiquitin Protein Ligases
Oximes / metabolism*
Phenylcarbamates / metabolism*
Ubiquitin-Protein Ligases / chemistry
Ubiquitin-Protein Ligases / metabolism*
Ubiquitination

Substances

Endosomal Sorting Complexes Required for Transport
Oximes
Phenylcarbamates
N-acetylglucosaminono-1,5-lactone O-(phenylcarbamoyl)oxime
Nedd4 Ubiquitin Protein Ligases
Nedd4 protein, human
Ubiquitin-Protein Ligases
N-Acetylglucosaminyltransferases
O-GlcNAc transferase
Caspases
Acetylglucosamine