Regulation of o‐linked n‐acetyl glucosamine transferase (Ogt) through e6 stimulation of the ubiquitin ligase activity of e6ap

Kangli Peng; Ruochuan Liu; Caiwei Jia; Yiyang Wang; Geon H. Jeong; Li Zhou; Ronggui Hu; Hiroaki Kiyokawa; Jun Yin; Bo Zhao

doi:10.3390/ijms221910286

Regulation of o‐linked n‐acetyl glucosamine transferase (Ogt) through e6 stimulation of the ubiquitin ligase activity of e6ap

Kangli Peng, Ruochuan Liu, Caiwei Jia, Yiyang Wang, Geon H. Jeong, Li Zhou, Ronggui Hu, Hiroaki Kiyokawa, Jun Yin^*, Bo Zhao^*

^*Corresponding author for this work

Pharmacology

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

Glycosyltransferase OGT catalyzes the conjugation of O‐linked β‐D‐N‐acetylglucosamine (O‐GlcNAc) to Ser and Thr residues of the cellular proteins and regulates many key processes in the cell. Here, we report the identification of OGT as a ubiquitination target of HECT‐type E3 ubiquitin (UB) ligase E6AP, whose overexpression in HEK293 cells would induce the degradation of OGT. We also found that the expression of E6AP in HeLa cells with the endogenous expression of the E6 protein of the human papillomavirus (HPV) would accelerate OGT degradation by the proteasome and suppress O‐GlcNAc modification of OGT substrates in the cell. Overall, our study establishes a new mechanism of OGT regulation by the ubiquitin–proteasome system (UPS) that mediates the crosstalk between protein ubiquitination and O‐GlcNAcylation pathways underlying diverse cellular processes.

Original language	English (US)
Article number	10286
Journal	International journal of molecular sciences
Volume	22
Issue number	19
DOIs	https://doi.org/10.3390/ijms221910286
State	Published - Oct 1 2021

Funding

Funding: This work was supported by grants from the Natural Science Foundation of China (31770921 and 31971187 to B.Z.), Science and Technology Commission of Shanghai Municipality Project (20JC1411200 to B.Z.), NIH (R01GM104498 to J.Y. and H.K.), and NSF (1710460 and 2109051 to J.Y.) of USA.

Keywords

E6
E6AP
Human papillomavirus
OGT
O‐GlcNAc
O‐GlcNAcylation
Ubiquitin
Ubiquitination

ASJC Scopus subject areas

Molecular Biology
Spectroscopy
Catalysis
Inorganic Chemistry
Computer Science Applications
Physical and Theoretical Chemistry
Organic Chemistry

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title = "Regulation of o‐linked n‐acetyl glucosamine transferase (Ogt) through e6 stimulation of the ubiquitin ligase activity of e6ap",

abstract = "Glycosyltransferase OGT catalyzes the conjugation of O‐linked β‐D‐N‐acetylglucosamine (O‐GlcNAc) to Ser and Thr residues of the cellular proteins and regulates many key processes in the cell. Here, we report the identification of OGT as a ubiquitination target of HECT‐type E3 ubiquitin (UB) ligase E6AP, whose overexpression in HEK293 cells would induce the degradation of OGT. We also found that the expression of E6AP in HeLa cells with the endogenous expression of the E6 protein of the human papillomavirus (HPV) would accelerate OGT degradation by the proteasome and suppress O‐GlcNAc modification of OGT substrates in the cell. Overall, our study establishes a new mechanism of OGT regulation by the ubiquitin–proteasome system (UPS) that mediates the crosstalk between protein ubiquitination and O‐GlcNAcylation pathways underlying diverse cellular processes.",

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author = "Kangli Peng and Ruochuan Liu and Caiwei Jia and Yiyang Wang and Jeong, {Geon H.} and Li Zhou and Ronggui Hu and Hiroaki Kiyokawa and Jun Yin and Bo Zhao",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

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doi = "10.3390/ijms221910286",

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T1 - Regulation of o‐linked n‐acetyl glucosamine transferase (Ogt) through e6 stimulation of the ubiquitin ligase activity of e6ap

AU - Peng, Kangli

AU - Liu, Ruochuan

AU - Jia, Caiwei

AU - Wang, Yiyang

AU - Jeong, Geon H.

AU - Zhou, Li

AU - Hu, Ronggui

AU - Kiyokawa, Hiroaki

AU - Yin, Jun

AU - Zhao, Bo

PY - 2021/10/1

Y1 - 2021/10/1

N2 - Glycosyltransferase OGT catalyzes the conjugation of O‐linked β‐D‐N‐acetylglucosamine (O‐GlcNAc) to Ser and Thr residues of the cellular proteins and regulates many key processes in the cell. Here, we report the identification of OGT as a ubiquitination target of HECT‐type E3 ubiquitin (UB) ligase E6AP, whose overexpression in HEK293 cells would induce the degradation of OGT. We also found that the expression of E6AP in HeLa cells with the endogenous expression of the E6 protein of the human papillomavirus (HPV) would accelerate OGT degradation by the proteasome and suppress O‐GlcNAc modification of OGT substrates in the cell. Overall, our study establishes a new mechanism of OGT regulation by the ubiquitin–proteasome system (UPS) that mediates the crosstalk between protein ubiquitination and O‐GlcNAcylation pathways underlying diverse cellular processes.

AB - Glycosyltransferase OGT catalyzes the conjugation of O‐linked β‐D‐N‐acetylglucosamine (O‐GlcNAc) to Ser and Thr residues of the cellular proteins and regulates many key processes in the cell. Here, we report the identification of OGT as a ubiquitination target of HECT‐type E3 ubiquitin (UB) ligase E6AP, whose overexpression in HEK293 cells would induce the degradation of OGT. We also found that the expression of E6AP in HeLa cells with the endogenous expression of the E6 protein of the human papillomavirus (HPV) would accelerate OGT degradation by the proteasome and suppress O‐GlcNAc modification of OGT substrates in the cell. Overall, our study establishes a new mechanism of OGT regulation by the ubiquitin–proteasome system (UPS) that mediates the crosstalk between protein ubiquitination and O‐GlcNAcylation pathways underlying diverse cellular processes.

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KW - E6AP

KW - Human papillomavirus

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KW - O‐GlcNAc

KW - O‐GlcNAcylation

KW - Ubiquitin

KW - Ubiquitination

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Regulation of o‐linked n‐acetyl glucosamine transferase (Ogt) through e6 stimulation of the ubiquitin ligase activity of e6ap

Abstract

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Keywords

ASJC Scopus subject areas

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