PBK/TOPK as a Potential Therapeutic Target in Glioblastoma and Other Malignancies


A serine/threonine kinase PDZ binding-kinase (PBK) is a member of the mitogen-activated protein kinase (MAPK) kinase (MAPKK) family [1-3]. This enzyme is also known under the name T-lymphokine-activated killer cell-originated protein kinase (TOPK). PBK was discovered as a factor that binds PDZ2 domain of hDLg (human homologue of the Drosophila Discs-large (Dlg) tumor suppressor protein) [2]. This study also demonstrated that the mitotic phosphorylation of PBK is required for its kinase activity [2]. Due to this specific activation during the mitotic-phase of the cell cycle, PBK is also denoted as a “mitotic kinase”. PBK protein is phosphorylated by cdk1/ cyclin B during mitosis and its presence is necessary for formation of the mid-zone of the mitotic spindle [3]. The PBK gene is especially highly expressed in placenta [2] and was also implicated in spermatogenesis [4,5]. Since PBK is expressed in seminiferous tubules of testis, where the male gametes are produced, it has been speculated that PBK might be essential in spermatocytogenesis during which mitosis occurs [4]. While PBK is not expressed in the adult human brain [2] its mRNA is abundant in the human fetal brain [4] and rapidly dividing neuronal stem/progenitor cells (NS/PCs) [6]. In mouse NS/PCs both Pbk and its downstream target p38 are essential for proliferation and self-renewal [6]. In the adult mouse brain, Pbk is expressed in rapidly proliferating NS/PCs of the adult subventricular zone and early postnatal cerebellar external granular layer [6]. The notion that PBK represents a stemnessassociated kinase is further supported by the evidence that PBK is down regulated during differentiation [6,7]. PBK is specifically expressed in all germinal zones during brain development and is not expressed in mature neurons and glial cells [6]. A study conducted in HL-60 myeloid leukemia cells, induced to differentiate, using phorbol ester, showed that PBK protein expression was strongly down-regulated in differentiated cells [7]. This study also showed that the expression of PBK correlated positively with the expression of a cell cycle regulator c-Myc.

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@inproceedings{Stangeland2016PBKTOPKAA, title={PBK/TOPK as a Potential Therapeutic Target in Glioblastoma and Other Malignancies}, author={Biljana Stangeland}, year={2016} }