ERK5/BMK1 Is a Novel Target of the Tumor Suppressor VHL: Implication in Clear Cell Renal Carcinoma

作者：Arias Gonzalez Laura; Moreno Gimeno Inmaculada; Rubio del Campo Antonio; Serrano Oviedo Leticia; Llanos Valero Maria; Esparis Ogando Azucena; Angel de la Cruz Morcillo Miguel; Melgar Rojas Pedro; Garcia Cano Jesus; Jose Cimas Francisco; Ruiz Hidalgo Maria Jose; Prado Alfonso; Luis Callejas Valera Juan; Hyun Nam Cha Syong; Miguel Gimenez Bachs Jose; Salinas Sanchez Antonio S; Pandiella Atanasio; del Peso Luis; Sanchez Prieto Ricardo^*

来源：NEOPLASIA, 2013, 15(6): 649-+.

DOI：10.1593/neo.121896

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.

• 出版日期2013-6