TOPK (T-lymphokine-activated killer cell–originated protein kinase, also known as PBK or PDZ-binding kinase) is a Ser/Thr protein kinase that is highly expressed in many types of human cancer, including breast and lung cancers. TOPK is included in the “consensus stemness ranking signature” gene list that is up-regulated in cancer stem cell-enriched tumors and is associated with poor prognosis in multiple types of cancer.

TOPK/PBK is an oncogenic kinase upregulated in most human cancers. TOPK is important for mitotic cell division and that phosphorylation by Cdk1 is needed for its activation.

TOPK, a member of the MEK3/6-related MAPKK family, is expressed in a wide range of proliferating cells and tissues, including cancer cells and testis. TOPK negatively regulates the activity of p38α by phosphorylating the p38α-specific phosphatase MKP1 and enhancing the stability of MKP1. The MAPK phosphatase MKP1, an archetypal member of the MKP family, plays a pivotal role in the deactivation of p38 through a dephosphorylation reaction.