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Title

Mxi2 promotes stimulus-independent ERK nuclear translocation

AuthorsCasar, Berta ; Sanz-Moreno, Victoria; Yazicioglu, Mustafa N.; Rodríguez, Javier; Berciano, María T.; Lafarga, Miguel; Cobb, Melanie H.; Crespo, Piero
KeywordsERK
MAP kinases
Mxi2
Nuclear import
Issue Date2007
PublisherNature Publishing Group
John Wiley & Sons
CitationEMBO Journal 26(3): 635-646 (2007)
AbstractSpatial 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 p38 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.
Publisher version (URL)http://dx.doi.org/10.1038/sj.emboj.7601523
URIhttp://hdl.handle.net/10261/49398
DOI10.1038/sj.emboj.7601523
ISSN0261-4189
Appears in Collections:(IBBTEC) Artículos
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