Non-Proteasomal UbL-UbA Family of Proteins in Neurodegeneration

Int J Mol Sci. 2019 Apr 17;20(8):1893. doi: 10.3390/ijms20081893.

Abstract

Ubiquitin-like/ubiquitin-associated proteins (UbL-UbA) are a well-studied family of non-proteasomal ubiquitin receptors that are evolutionarily conserved across species. Members of this non-homogenous family facilitate and support proteasomal activity by promoting different effects on proteostasis but exhibit diverse extra-proteasomal activities. Dysfunctional UbL-UbA proteins render cells, particularly neurons, more susceptible to stressors or aging and may cause earlier neurodegeneration. In this review, we summarized the properties and functions of UbL-UbA family members identified to date, with an emphasis on new findings obtained using Drosophila models showing a direct or indirect role in some neurodegenerative diseases.

Keywords: Drosophila; UbL-UbA; neurodegenerative diseases; non-proteasomal ubiquitin receptor; proteostasis; ubiquitin-like.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Autophagy-Related Proteins
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins / metabolism
  • DNA Repair Enzymes / metabolism
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Drosophila
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Neurons / metabolism
  • Neurons / pathology*
  • Proteasome Endopeptidase Complex / metabolism
  • Proteostasis
  • Transcription Factors / metabolism
  • Ubiquitin / metabolism*
  • Ubiquitin-Protein Ligases
  • Ubiquitins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Autophagy-Related Proteins
  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • NUB1 protein, human
  • Transcription Factors
  • UBQLN1 protein, human
  • Ubiquitin
  • Ubiquitins
  • RAD23A protein, human
  • UBAC1 protein, human
  • Ubiquitin-Protein Ligases
  • Proteasome Endopeptidase Complex
  • DNA Repair Enzymes