2. Academic Validation
  3. O-GlcNAc regulates NEDD4-1 stability via caspase-mediated pathway

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.
Kuan Jiang 1,  Bingyang Bai 1,  Yajie Ta 1,  Tingling Zhang 1,  Zikang Xiao 1,  Peng George Wang 2,  Lianwen Zhang 3
Affiliations

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.

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