ERK and JNK activation is essential for oncogenic transformation by v-Rel

作者：Kralova J; Sheely J I; Liss A S; Bose H R Jr^*

来源：Oncogene, 2010, 29(47): 6267-6279.

DOI：10.1038/onc.2010.359

• v-Rel
• NF-kappa B
• transformation
• oncogenesis
• MAPK

v-Rel is the acutely oncogenic member of the NF-kappa B family of transcription factors. Infection with retroviruses expressing v-Rel rapidly induces fatal lymphomas in birds and transforms primary lymphocytes and fibroblasts in vitro. We have previously shown that AP-1 transcriptional activity contributes to v-Rel-mediated transformation. Although v-Rel increases the expression of these factors, their activity may also be induced through phosphorylation by the mitogen-activated protein kinases (MAPKs). The expression of v-Rel results in the strong and sustained activation of the ERK and JNK MAPK pathways. This induction is critical for the v-Rel-transformed phenotype, as suppression of MAPK activity with chemical inhibitors or small interfering RNA severely impairs colony formation of v-Rel-transformed lymphoid cell lines. However, signaling must be maintained within an optimal range in these cells, as strong additional activation of either pathway beyond the levels induced by v-Rel through the expression of constitutively active MAPK proteins attenuates the transformed phenotype. MAPK signaling also has an important role in the initial transformation of primary spleen cells by v-Rel, although distinct requirements for MAPK activity at different stages of v-Rel-mediated transformation were identified. We also show that the ability of v-Rel to induce MAPK signaling more strongly than c-Rel contributes to its greater oncogenicity. Oncogene (2010) 29, 6267-6279; doi:10.1038/onc.2010.359; published online 30 August 2010

• 出版日期2010-11