Deubiquitinating enzymes in cellular signaling and disease regulation

IUBMB Life. 2015 Jul;67(7):544-55. doi: 10.1002/iub.1402. Epub 2015 Jul 14.

Abstract

Protein post-translational modification by ubiquitin represents a complex signaling system that regulates many cellular events including proteostasis to intercellular communications. Deubiquitinating enzymes (DUBs) that specifically disassemble Ub-chains or regulate ubiquitin homeostasis reside as a central component in ubiquitin signaling. Human genome encodes almost 100 DUBs and majority of them are not well characterized. Considerable progress has been made in the understanding of enzymatic mechanism; however, their cellular substrate specificity and regulation are largely unknown. Involvement of DUBs in disease regulation has been depicted since its discovery and several attempts have been made for evaluating DUBs as a drug target. In this review, we have updated briefly a new insight of DUBs activity, their cellular role, disease regulation, and therapeutic potential.

Keywords: cysteine proteases; deubiquitinating enzymes; enzyme mechanisms; neurodegenerative disorders; signaling; ubiquitin-proteasome system.

Publication types

  • Review

MeSH terms

  • DNA Damage
  • DNA Repair
  • Enzymes / chemistry
  • Enzymes / metabolism*
  • Humans
  • Neoplasms / metabolism*
  • Neurodegenerative Diseases / metabolism
  • Oxidation-Reduction
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Ribosomal Proteins / metabolism
  • Signal Transduction
  • Stem Cells / metabolism*
  • Substrate Specificity
  • Sumoylation
  • Ubiquitin / metabolism*
  • Ubiquitination
  • Ubiquitins / metabolism

Substances

  • Enzymes
  • RPS27a protein, human
  • Ribosomal Proteins
  • UBB protein, human
  • Ubiquitin
  • Ubiquitins