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Title

ERK5/BMK1 is a novel target of the tumor suppressor VHL: Implication in clear cell renal carcinoma

AuthorsEsparís-Ogando, Azucena ; Prado, Alfonso; Pandiella, Atanasio ; Peso, Luis del; Sánchez-Prieto, Ricardo
Issue Date2013
PublisherElsevier
CitationNeoplasia 15(6): 649-659 (2013)
AbstractExtracellular signal-regulated kinase 5 (ERK5), also known as big mitogen-activated protein kinase (MAPK) 1, is implicated in a wide range of biologic processes, which include proliferation or vascularization. Here, we show that ERK5 is degraded through the ubiquitin-proteasome system, in a process mediated by the tumor suppressor von Hippel-Lindau (VHL) gene, through a prolyl hydroxylation-dependent mechanism. Our conclusions derive from transient transfection assays in Cos7 cells, as well as the study of endogenous ERK5 in different experimental systems such as MCF7, HMEC, or Caki-2 cell lines. In fact, the specific knockdown of ERK5 in pVHL-negative cell lines promotes a decrease in proliferation and migration, supporting the role of this MAPK in cellular transformation. Furthermore, in a short series of fresh samples from human clear cell renal cell carcinoma, high levels of ERK5 correlate with more aggressive and metastatic stages of the disease. Therefore, our results provide new biochemical data suggesting that ERK5 is a novel target of the tumor suppressor VHL, opening a new field of research on the role of ERK5 in renal carcinomas.
DescriptionUnder a Creative Commons license.-- et al.
Publisher version (URL)http://dx.doi.org/10.1593/neo.121896
URIhttp://hdl.handle.net/10261/123904
DOI10.1593/neo.121896
Identifiersissn: 1522-8002
e-issn: 1476-5586
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