Fine-Tuning Limited Proteolysis: A Major Role for Regulated Site-Specific O-Glycosylation

Christoffer K. Goth; Sergey Y. Vakhrushev; Hiren J. Joshi; Henrik Clausen; Katrine T. Schjoldager

doi:10.1016/j.tibs.2018.02.005

Fine-Tuning Limited Proteolysis: A Major Role for Regulated Site-Specific O-Glycosylation

Christoffer K. Goth^*, Sergey Y. Vakhrushev, Hiren J. Joshi, Henrik Clausen, Katrine T. Schjoldager

^*Corresponding author af dette arbejde

Glycomics Program

21 Citationer (Scopus)

Abstract

Limited proteolytic processing is an essential and ubiquitous post-translational modification (PTM) affecting secreted proteins; failure to regulate the process is often associated with disease. Glycosylation is also a ubiquitous protein PTM and site-specific O-glycosylation in close proximity to sites of proteolysis can regulate and direct the activity of proprotein convertases, a disintegrin and metalloproteinases (ADAMs), and metalloproteinases affecting the activation or inactivation of many classes of proteins, including G-protein-coupled receptors (GPCRs). Here, we summarize the emerging data that suggest O-glycosylation to be a key regulator of limited proteolysis, and highlight the potential for crosstalk between multiple PTMs.

Originalsprog	Engelsk
Tidsskrift	Trends in Biochemical Sciences
Vol/bind	43
Udgave nummer	4
Sider (fra-til)	269-284
Antal sider	16
ISSN	0968-0004
DOI	https://doi.org/10.1016/j.tibs.2018.02.005
Status	Udgivet - 2018

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10.1016/j.tibs.2018.02.005

Citationsformater

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title = "Fine-Tuning Limited Proteolysis: A Major Role for Regulated Site-Specific O-Glycosylation",

abstract = "Limited proteolytic processing is an essential and ubiquitous post-translational modification (PTM) affecting secreted proteins; failure to regulate the process is often associated with disease. Glycosylation is also a ubiquitous protein PTM and site-specific O-glycosylation in close proximity to sites of proteolysis can regulate and direct the activity of proprotein convertases, a disintegrin and metalloproteinases (ADAMs), and metalloproteinases affecting the activation or inactivation of many classes of proteins, including G-protein-coupled receptors (GPCRs). Here, we summarize the emerging data that suggest O-glycosylation to be a key regulator of limited proteolysis, and highlight the potential for crosstalk between multiple PTMs.",

keywords = "G-protein-coupled receptors, GalNAc-Ts, O-glycosylation, proteases, proteolytic processing, PTM",

author = "Goth, {Christoffer K.} and Vakhrushev, {Sergey Y.} and Joshi, {Hiren J.} and Henrik Clausen and Schjoldager, {Katrine T.}",

year = "2018",

doi = "10.1016/j.tibs.2018.02.005",

language = "English",

volume = "43",

pages = "269--284",

journal = "Trends in Biochemical Sciences",

issn = "0968-0004",

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TY - JOUR

T1 - Fine-Tuning Limited Proteolysis

T2 - A Major Role for Regulated Site-Specific O-Glycosylation

AU - Goth, Christoffer K.

AU - Vakhrushev, Sergey Y.

AU - Joshi, Hiren J.

AU - Clausen, Henrik

AU - Schjoldager, Katrine T.

PY - 2018

Y1 - 2018

N2 - Limited proteolytic processing is an essential and ubiquitous post-translational modification (PTM) affecting secreted proteins; failure to regulate the process is often associated with disease. Glycosylation is also a ubiquitous protein PTM and site-specific O-glycosylation in close proximity to sites of proteolysis can regulate and direct the activity of proprotein convertases, a disintegrin and metalloproteinases (ADAMs), and metalloproteinases affecting the activation or inactivation of many classes of proteins, including G-protein-coupled receptors (GPCRs). Here, we summarize the emerging data that suggest O-glycosylation to be a key regulator of limited proteolysis, and highlight the potential for crosstalk between multiple PTMs.

AB - Limited proteolytic processing is an essential and ubiquitous post-translational modification (PTM) affecting secreted proteins; failure to regulate the process is often associated with disease. Glycosylation is also a ubiquitous protein PTM and site-specific O-glycosylation in close proximity to sites of proteolysis can regulate and direct the activity of proprotein convertases, a disintegrin and metalloproteinases (ADAMs), and metalloproteinases affecting the activation or inactivation of many classes of proteins, including G-protein-coupled receptors (GPCRs). Here, we summarize the emerging data that suggest O-glycosylation to be a key regulator of limited proteolysis, and highlight the potential for crosstalk between multiple PTMs.

KW - G-protein-coupled receptors

KW - GalNAc-Ts

KW - O-glycosylation

KW - proteases

KW - proteolytic processing

KW - PTM

U2 - 10.1016/j.tibs.2018.02.005

DO - 10.1016/j.tibs.2018.02.005

M3 - Review

C2 - 29506880

AN - SCOPUS:85042631647

SN - 0968-0004

VL - 43

SP - 269

EP - 284

JO - Trends in Biochemical Sciences

JF - Trends in Biochemical Sciences

IS - 4

ER -

Fine-Tuning Limited Proteolysis: A Major Role for Regulated Site-Specific O-Glycosylation

Abstract

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