PME-1 is regulated by USP36 in ERK and Akt signaling pathways

FEBS Lett. 2018 May;592(9):1575-1588. doi: 10.1002/1873-3468.13039. Epub 2018 Apr 10.

Abstract

Deubiquitinating enzymes (DUBs) play an important role in the ubiquitin-proteasome system (UPS) by eliminating ubiquitins from substrates and inhibiting proteasomal degradation. Protein phosphatase methylesterase 1 (PME-1) inactivates protein phosphatase 2A (PP2A) and enhances the ERK and Akt signaling pathways, which increase cell proliferation and malignant cell transformation. In this study, we demonstrate that USP36 regulates PME-1 through its deubiquitinating enzyme activity. USP36 increases PME-1 stability, and depletion of USP36 decreases the PME-1 expression level. Furthermore, we demonstrate that USP36 promotes the ERK and Akt signaling pathways. In summary, it is suggested that USP36 regulates PME-1 as a DUB and participates in the ERK and Akt signaling pathways.

Keywords: Akt signaling pathway; ERK signaling pathway; Malignant transformation; USP36; deubiquitinating enzyme; ubiquitination.

Publication types

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

MeSH terms

  • Carboxylic Ester Hydrolases / metabolism*
  • Disease Progression
  • Enzyme Stability
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Domains
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction*
  • Ubiquitin / metabolism
  • Ubiquitin Thiolesterase / chemistry
  • Ubiquitin Thiolesterase / metabolism*

Substances

  • USP36 protein, human
  • Ubiquitin
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • Carboxylic Ester Hydrolases
  • protein phosphatase methylesterase-1
  • Ubiquitin Thiolesterase
  • Proteasome Endopeptidase Complex