From interactomics to cancer cell proliferation: Regulation of MAP kinase ERK5 by oncogenic chaperones
Speaker: José Miguel Lizcano
Universidad Autónoma de Barcelona (NeuroKinase Lab - Institut of Neuroscience; Faculty of Medicine)
Host: Atanasio Pandiella
Salón de Actos del CICFrom interactomics to cancer cell proliferation: Regulation of MAP kinase ERK5 by oncogenic chaperones
The MAP kinase ERK5 plays a crucial role in cell proliferation, regulating gene transcription by phosphorylating transcription factors and acting itself as a transcriptional coactivator. ERK5 is necessary for proliferation of several cancers. Among others, ERK5 plays a role in the progression and invasivity of human prostate cancer. However, the precise molecular mechanisms regulating ERK5 nuclear translocation and transcriptional activation remain to be described.
Using tandem affinity (TAP) purification, nLC-MS/MS and biochemical analysis we show that cytosolic ERK5 interacts with chaperons Hsp90 and Cdc37 in resting cells, and that activation of ERK5 induces Hsp90 dissociation prior to ERK5 nuclear translocation. More importantly, overexpression of the oncogenic chaperone Cdc37 (as it happens in human prostate cancer) induces ERK5-mediated AP1 transcriptional activity without affecting kinase activity. Furthermore, Cdc37 collaborates with ERK5 to promote cell proliferation, migration and invasivity in stable prostate cancer PC-3 cells. Finally, I will present preliminary data showing a biochemical and functional interaction of ERK5 with the androgen receptor, a protein that plays a pivotal role in prostate cancer.