Mechanisms of regulation and diversification of deubiquitylating enzyme function

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

Research output: Contribution to journalComment/debatepeer-review

74 Citations (Scopus)
267 Downloads (Pure)


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
Early online date5 May 2017
Publication statusPublished - 15 Jun 2017


  • Deubiquitinase
  • Signal transduction
  • Ubiquitylation
  • Deubiquitylase


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