Mechanisms of regulation and diversification of deubiquitylating enzyme function

Pawel Leznicki (Lead / Corresponding author), Yogesh Kulathu (Lead / Corresponding author)

Research output: Contribution to journalComment/debate

19 Citations (Scopus)
82 Downloads (Pure)

Abstract

Deubiquitinating enzymes (DUBs) are proteases that reverse protein ubiquitylation and therefore modulate the outcome of this posttranslational modification. DUBs regulate a variety of intracellular processes, including protein turnover, signalling pathways and the DNA damage response. They have also been linked to a number of human diseases, such as cancer, and inflammatory and neurodegenerative disorders. Although we are beginning to better appreciate the role of DUBs in basic cell biology and their importance for human health, there are still many unknowns. Central among these is the conundrum of how the small number of ∼100 DUBs encoded in the human genome is capable of regulating the thousands of ubiquitin modification sites detected at steady-state conditions in human cells. This Commentary addresses the biological mechanisms employed to modulate and expand the functions of DUBs, and sets directions for future research aimed at elucidating the details of these fascinating processes.
Original languageEnglish
Pages (from-to)1997-2006
Number of pages10
JournalJournal of Cell Science
Volume130
Early online date5 May 2017
DOIs
Publication statusPublished - 15 Jun 2017

Fingerprint

Enzymes
Ubiquitination
Human Genome
Post Translational Protein Processing
Ubiquitin
Neurodegenerative Diseases
DNA Damage
Cell Biology
Proteins
Peptide Hydrolases
Health
Neoplasms
Deubiquitinating Enzymes
Direction compound

Keywords

  • Deubiquitinase
  • Signal transduction
  • Ubiquitylation
  • Deubiquitylase

Cite this

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abstract = "Deubiquitinating enzymes (DUBs) are proteases that reverse protein ubiquitylation and therefore modulate the outcome of this posttranslational modification. DUBs regulate a variety of intracellular processes, including protein turnover, signalling pathways and the DNA damage response. They have also been linked to a number of human diseases, such as cancer, and inflammatory and neurodegenerative disorders. Although we are beginning to better appreciate the role of DUBs in basic cell biology and their importance for human health, there are still many unknowns. Central among these is the conundrum of how the small number of ∼100 DUBs encoded in the human genome is capable of regulating the thousands of ubiquitin modification sites detected at steady-state conditions in human cells. This Commentary addresses the biological mechanisms employed to modulate and expand the functions of DUBs, and sets directions for future research aimed at elucidating the details of these fascinating processes.",
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Mechanisms of regulation and diversification of deubiquitylating enzyme function. / Leznicki, Pawel (Lead / Corresponding author); Kulathu, Yogesh (Lead / Corresponding author).

In: Journal of Cell Science, Vol. 130, 15.06.2017, p. 1997-2006.

Research output: Contribution to journalComment/debate

TY - JOUR

T1 - Mechanisms of regulation and diversification of deubiquitylating enzyme function

AU - Leznicki, Pawel

AU - Kulathu, Yogesh

N1 - Work in the Kulathu laboratory is supported by the Medical Research Council, UK (MC_UU_12016/6, Ubiquitin signaling mechanisms), Tenovus Scotland, European Molecular Biology Organization (EMBO) Young Investigator Programme and the European Research Council (677623).

PY - 2017/6/15

Y1 - 2017/6/15

N2 - Deubiquitinating enzymes (DUBs) are proteases that reverse protein ubiquitylation and therefore modulate the outcome of this posttranslational modification. DUBs regulate a variety of intracellular processes, including protein turnover, signalling pathways and the DNA damage response. They have also been linked to a number of human diseases, such as cancer, and inflammatory and neurodegenerative disorders. Although we are beginning to better appreciate the role of DUBs in basic cell biology and their importance for human health, there are still many unknowns. Central among these is the conundrum of how the small number of ∼100 DUBs encoded in the human genome is capable of regulating the thousands of ubiquitin modification sites detected at steady-state conditions in human cells. This Commentary addresses the biological mechanisms employed to modulate and expand the functions of DUBs, and sets directions for future research aimed at elucidating the details of these fascinating processes.

AB - Deubiquitinating enzymes (DUBs) are proteases that reverse protein ubiquitylation and therefore modulate the outcome of this posttranslational modification. DUBs regulate a variety of intracellular processes, including protein turnover, signalling pathways and the DNA damage response. They have also been linked to a number of human diseases, such as cancer, and inflammatory and neurodegenerative disorders. Although we are beginning to better appreciate the role of DUBs in basic cell biology and their importance for human health, there are still many unknowns. Central among these is the conundrum of how the small number of ∼100 DUBs encoded in the human genome is capable of regulating the thousands of ubiquitin modification sites detected at steady-state conditions in human cells. This Commentary addresses the biological mechanisms employed to modulate and expand the functions of DUBs, and sets directions for future research aimed at elucidating the details of these fascinating processes.

KW - Deubiquitinase

KW - Signal transduction

KW - Ubiquitylation

KW - Deubiquitylase

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DO - 10.1242/jcs.201855

M3 - Comment/debate

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VL - 130

SP - 1997

EP - 2006

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

ER -