SUMOylation Is Required for ERK5 Nuclear Translocation and ERK5-Mediated Cancer Cell Proliferation
Erazo, Tatiana (Universitat Autònoma de Barcelona. Institut de Neurociències)
Espinosa-Gil, Sergio (Universitat Autònoma de Barcelona. Institut de Neurociències)
Diéguez-Martínez, Nora (Universitat Autònoma de Barcelona. Institut de Neurociències)
Gomez, Nestor (Universitat Autònoma de Barcelona. Institut de Neurociències)
Lizcano de Vega, José Miguel (Universitat Autònoma de Barcelona. Institut de Neurociències)

Date:	2020
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.
Grants:	Ministerio de Educación y Ciencia BFU2007-60268 Ministerio de Economía y Competitividad SAF2015-64237-R
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	International journal of molecular sciences, Vol. 21 (2020) , ISSN 1422-0067

DOI: 10.3390/ijms21062203
PMID: 32209980

18 p, 2.7 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles