Protein kinase CK2 in health and disease: CK2: the kinase controlling the Hsp90 chaperone machinery.
CK2 is a ubiquitous and essential protein kinase with pleiotropic substrates and function, but it remains unclear how, when, and where CK2 activity is regulated in cells. Hsp90 is a major molecular chaperone that is required for the folding and function of its client proteins. A complex containing Hsp90 and its client protein includes co-chaperones such as steroid hormone receptor-specific FKBP52 and signaling kinase-specific Cdc37. Co-chaperones work cooperatively with Hsp90 to stabilize client proteins and to keep them in a conformation amenable to activation under appropriate conditions. In this review, critical roles of CK2 in the regulation of the Hsp90-mediated chaperone system are described. CK2 phosphorylates and modulates Hsp90 and its co-chaperones FKBP52 and Cdc37. CK2-dependent phosphorylation of Cdc37 is essential for the chaperoning function of Hsp90-Cdc37 for multiple signaling protein kinases. The tumor kinome appears to become addicted to the Hsp90-Cdc37 chaperone system, thus, targeting Hsp90, Cdc37, and CK2 is a promising strategy for cancer treatment.
Miyata
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Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto, 606 - 8502, Japan. ymiyata@lif.kyoto-u.ac.jp
D000595:Amino Acid Sequence; D000818:Animals; D047390:Casein Kinase II / Q000737:chemistry / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018833:Chaperonins / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry / Q000502:physiology*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D022021:Tacrolimus Binding Proteins / Q000378:metabolism*
C498362:CDC37 protein, human; D018797:Cell Cycle Proteins; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D047390:Casein Kinase II; D018833:Chaperonins; D022021:Tacrolimus Binding Proteins; C403485:tacrolimus binding protein 4