The pivotal role of ubiquitin-activating enzyme E1 (UBA1) in neuronal health and neurodegeneration

Int J Biochem Cell Biol. 2020 Jun:123:105746. doi: 10.1016/j.biocel.2020.105746. Epub 2020 Apr 18.


Ubiquitin-activating enzyme E1, UBA1, functions at the apex of the enzymatic ubiquitylation cascade, catalysing ubiquitin activation. UBA1 is thus of fundamental importance to the modulation of ubiquitin homeostasis and to all downstream ubiquitylation-dependent cellular processes, including proteolysis through the ubiquitin-proteasome system and selective autophagy. The proteasome-dependent and -independent functions of UBA1 contribute significantly to a range of processes crucial to neuronal health. The significance of UBA1 activity to neuronal health is clear in light of accumulating evidence implicating impaired UBA1 activity in a range of neurodegenerative conditions, including Parkinson's disease, Alzheimer's disease, Huntington's disease and spinal muscular atrophy. Moreover, ubiquitylation-independent functions of UBA1 of importance to neuronal functioning have been proposed. Here, we summarise findings supporting the significant role of UBA1 in regulating neuronal functioning, and discuss the detrimental consequences of UBA1 impairment that contribute to neuronal dysfunction and degeneration.

Keywords: Motor neuron; Neurodegeneration; Ubiquitin-activating enzyme E1; Ubiquitylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autophagy / genetics
  • Humans
  • Motor Neurons / metabolism
  • Muscular Atrophy, Spinal / genetics
  • Muscular Atrophy, Spinal / metabolism
  • Muscular Atrophy, Spinal / physiopathology
  • Neurodegenerative Diseases / enzymology*
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / physiopathology
  • Neurodegenerative Diseases / therapy
  • Neurons / enzymology*
  • Neurons / metabolism
  • Signal Transduction / genetics
  • Ubiquitin / metabolism
  • Ubiquitin-Activating Enzymes / chemistry
  • Ubiquitin-Activating Enzymes / genetics
  • Ubiquitin-Activating Enzymes / metabolism*
  • Ubiquitin-Activating Enzymes / physiology
  • Ubiquitination* / genetics


  • Ubiquitin
  • Ubiquitin-Activating Enzymes