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Numerous proteins with unique characteristics are degraded by the 26S proteasome following monoubiquitination

Ori Braten1, Ido Livneh1, Tamar Ziv2

  • 1Technion Integrated Cancer Center, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, 3109602, Israel;

Proceedings of the National Academy of Sciences of the United States of America
|July 8, 2016
PubMed

Insights

Monoubiquitination targets proteins for proteasomal degradation, independent of polyubiquitin chains. This pathway is more common than previously thought and involves smaller, less disordered proteins.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The canonical proteasomal degradation pathway relies on polyubiquitin chains.
  • However, some proteins are degraded via monoubiquitination.

Purpose of the Study:

  • To systematically identify monoubiquitination-dependent proteasomal substrates in human and yeast cells.
  • To characterize the features distinguishing monoubiquitinated from polyubiquitinated substrates.

Main Methods:

  • Replaced wild-type polymerizable ubiquitin with non-chain-forming ubiquitin.
  • Utilized proteomic analysis to screen for substrates degraded or stabilized under these conditions.
  • Confirmed substrate stability predictions for representative samples.

Main Results:

  • Identified distinct groups of monoubiquitinated and polyubiquitinated proteasomal substrates.
  • Monoubiquitinated substrates are generally smaller and structurally less disordered (in humans).
  • Monoubiquitinated substrates are enriched in specific cellular pathways.

Conclusions:

  • Monoubiquitination-dependent proteasomal degradation is a significant and widespread cellular process.
  • This pathway targets specific protein classes and plays crucial roles in cellular functions.
  • The findings expand our understanding of protein degradation mechanisms beyond polyubiquitination.
Keywords:
26S proteasomemonoubiquitinationprotein degradationubiquitin replacement

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