Mxi2 promotes stimulus-independent ERK nuclear translocation

Berta Casar, Victoria Sanz-Moreno, Mustafa N. Yazicioglu, Javier Rodríguez, María T. Berciano, Miguel Lafarga, Melanie H. Cobb, Piero Crespo

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Spatial regulation of ERK1/2 MAP kinases is an essential yet largely unveiled mechanism for ensuring the fidelity and specificity of their signals. Mxi2 is a p38α isoform with the ability to bind ERK1/2. Herein we show that Mxi2 has profound effects on ERK1/2 nucleocytoplasmic distribution, promoting their accumulation in the nucleus. Downregulation of endogenous Mxi2 by RNAi causes a marked reduction of ERK1/2 in the nucleus, accompanied by a pronounced decline in cellular proliferation. We demonstrate that Mxi2 functions in nuclear shuttling of ERK1/2 by enhancing the nuclear accumulation of both phosphorylated and unphosphorylated forms in the absence of stimulation. This process requires the direct interaction of both proteins and a high-affinity binding of Mxi2 to ERK-binding sites in nucleoporins, In this respect, Mxi2 acts antagonistically to PEA15, displacing it from ERK1/2 complexes. These results point to Mxi2 as a key spatial regulator for ERK1/2 and disclose an unprecedented stimulus-independent mechanism for ERK nuclear import.

Original languageEnglish (US)
Pages (from-to)635-646
Number of pages12
JournalEMBO Journal
Volume26
Issue number3
DOIs
StatePublished - Feb 7 2007

Keywords

  • ERK
  • MAP kinases
  • Mxi2
  • Nuclear import
  • p38

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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  • Cite this

    Casar, B., Sanz-Moreno, V., Yazicioglu, M. N., Rodríguez, J., Berciano, M. T., Lafarga, M., Cobb, M. H., & Crespo, P. (2007). Mxi2 promotes stimulus-independent ERK nuclear translocation. EMBO Journal, 26(3), 635-646. https://doi.org/10.1038/sj.emboj.7601523