Targeting the BMK1 MAP Kinase Pathway in Cancer Therapy

The activated BMK1 MAPK cascade promotes cell cycle progression of tumor cells induced by mitogens and/or oncogenic signals. The BMK1 pathway is activated by mitogens and oncogenic signals through a 3-level kinase cascade (MEKK2 or MEKK3/MEK5/BMK1). Subsequently, activated BMK1 phosphorylates and suppresses the activity of its downstream effector PML, thereby promoting the S-phase entry of tumor cells. Some tumor cells upregulate BMK1 activity by overexpression of MEK5, which consequently augments their metastatic and chemoresistant potentials. In mitotic tumor cells, it was reported that CDK is involved in phosphorylating and regulating BMK1 in a MEK5-independent manner. PML-NB, PML nuclear body.