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

Extracellular 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...

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Detalhes bibliográficos
Autores: Arias González, Laura, Moreno Gimeno, Inmaculada, Rubio del Campo, Antonio, Serrano Oviedo, Leticia, Valero, María Llanos, Esparís Ogando, Azucena, Cruz Morcillo, Miguel Ángel de la, Melgar Rojas, Pedro, García Cano, Jesús, Cimas Felipe, Francisco José, Ruiz Hidalgo, María José, Prado, Alfonso, Callejas Valera, Juan Luis, Nam-Cha, Syong Hyun, Giménez Bachs, José Miguel, Salinas Sánchez, Antonio S., Pandiella, Atanasio, Peso, Luis del, Sánchez Prieto, Ricardo
Tipo de documento: artigo
Data de publicação:2013
País:España
Recursos:Fundación Dialnet. Universidad de La Rioja
Repositório:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/48003
Acesso em linha:https://hdl.handle.net/10578/48003
Access Level:Acceso aberto
Palavra-chave:Clear cell renal carcinoma
Extracellular signal–regulated kinase 5 (ERK5)
Tumor suppressor von Hippel-Lindau (VHL) gene
Descrição
Resumo:Extracellular 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.

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