SUMOylation Is Required for ERK5 Nuclear Translocation and ERK5-Mediated Cancer Cell Proliferation

Tatiana Erazo, Sergio Espinosa-Gil, Nora Diéguez-Martínez, Néstor Gómez, Jose M. Lizcano

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

The MAP kinase ERK5 contains an N-terminal kinase domain and a unique C-terminal tail including a nuclear localization signal and a transcriptional activation domain. ERK5 is activated in response to growth factors and stresses and regulates transcription at the nucleus by either phosphorylation or interaction with transcription factors. MEK5-ERK5 pathway plays an important role regulating cancer cell proliferation and survival. Therefore, it is important to define the precise molecular mechanisms implicated in ERK5 nucleo-cytoplasmic shuttling. We previously described that the molecular chaperone Hsp90 stabilizes and anchors ERK5 at the cytosol and that ERK5 nuclear shuttling requires Hsp90 dissociation. Here, we show that MEK5 or overexpression of Cdc37-mechanisms that increase nuclear ERK5-induced ERK5 Small Ubiquitin-related Modifier (SUMO)-2 modification at residues Lys6/Lys22 in cancer cells. Furthermore, mutation of these SUMO sites abolished the ability of ERK5 to translocate to the nucleus and to promote prostatic cancer PC-3 cell proliferation. We also show that overexpression of the SUMO protease SENP2 completely abolished endogenous ERK5 nuclear localization in response to epidermal growth factor (EGF) stimulation. These results allow us to propose a more precise mechanism: in response to MEK5 activation, ERK5 SUMOylation favors the dissociation of Hsp90 from the complex, allowing ERK5 nuclear shuttling and activation of the transcription.

Original languageAmerican English
JournalInternational Journal of Molecular Sciences
Volume21
Issue number6
DOIs
Publication statusPublished - 23 Mar 2020

Keywords

  • Bmk1
  • cancer
  • Cdc37
  • cell proliferation
  • ERK5
  • Hsp90
  • MAP kinase
  • nuclear translocation
  • SUMO
  • transcription

Fingerprint

Dive into the research topics of 'SUMOylation Is Required for ERK5 Nuclear Translocation and ERK5-Mediated Cancer Cell Proliferation'. Together they form a unique fingerprint.

Cite this