The protein CAK1, found in Saccharomyces cerevisiae, is a cyclin-dependent kinase-activating kinase (CAK) that plays a crucial role in cell cycle regulation and other cellular processes. CAK1 is responsible for activating the Cdc28p cyclin-dependent kinase (CDK) by phosphorylating threonine-169 in its activation loop [1]. This activation of Cdc28p is essential for cell cycle progression and chromosome stability [2]. Additionally, CAK1 has been found to promote meiosis and spore formation in a CDC28-independent manner [3]. Furthermore, CAK1 has been shown to functionally interact with the PAF1 complex and phosphatase Ssu72 via kinases Ctk1 and Bur1, demonstrating its involvement in various cellular pathways [4]. It is also known to activate two other CDKs in yeast by phosphorylating a threonine within their conserved T-loop domains [5].
CAK1 has been identified as an unusual 44-kilodalton protein kinase that is only distantly related to CDKs [6]. It is the physiological CAK in budding yeast and localizes to the cytoplasm [6]. The sole essential function of CAK1 is to phosphorylate Cdc28p, and its synthetic lethality with certain phosphatases is due to the inactivation of Cdc28p [7]. Moreover, CAK1 has been found to engage in stable, mutation-reinforced association with the most atypical member of the yeast kinome, Cdk-activating kinase (Cak1) [8].
References:
[1] F. Espinoza, A. Farrell, H. Erdjument‐Bromage, P. Tempst, & D. Morgan, "A cyclin-dependent kinase-activating kinase (cak) in budding yeast unrelated to vertebrate cak", Science, vol. 273, no. 5282, p. 1714-1717, 1996. https://doi.org/10.1126/science.273.5282.1714
[2] A. Kitazono and S. Kron, "An essential function of yeast cyclin-dependent kinase cdc28 maintains chromosome stability", Journal of Biological Chemistry, vol. 277, no. 50, p. 48627-48634, 2002. https://doi.org/10.1074/jbc.m207247200
[3] M. Schaber, A. Lindgren, K. Schindler, D. Bungard, P. Kaldis, & E. Winter, "cak1 promotes meiosis and spore formation in saccharomyces cerevisiae in a cdc28-independent fashion", Molecular and Cellular Biology, vol. 22, no. 1, p. 57-68, 2002. https://doi.org/10.1128/mcb.22.1.57-68.2002
[4] C. Ganem, C. Miled, C. Facca, J. Valay, G. Labesse, S. Hassineet al., "Kinase cak1 functionally interacts with the paf1 complex and phosphatase ssu72 via kinases ctk1 and bur1", Molecular Genetics and Genomics, vol. 275, no. 2, p. 136-147, 2005. https://doi.org/10.1007/s00438-005-0071-y
[5] S. Yao and G. Prelich, "Activation of the bur1-bur2 cyclin-dependent kinase complex by cak1", Molecular and Cellular Biology, vol. 22, no. 19, p. 6750-6758, 2002. https://doi.org/10.1128/mcb.22.19.6750-6758.2002
[6] P. Kaldis, "The cdk-activating kinase (cak): from yeast to mammals", Cellular and Molecular Life Sciences, vol. 55, no. 2, p. 284-296, 1999. https://doi.org/10.1007/s000180050290
[7] A. Cheng, K. Ross, P. Kaldis, & M. Solomon, "Dephosphorylation of cyclin-dependent kinases by type 2c protein phosphatases", Genes & Development, vol. 13, no. 22, p. 2946-2957, 1999. https://doi.org/10.1101/gad.13.22.2946
[8] S. Millson, P. Oosten-Hawle, M. Alkuriji, A. Truman, M. Siderius, & P. Piper, "Cdc37 engages in stable, s14a mutation-reinforced association with the most atypical member of the yeast kinome, cdk-activating kinase (cak1)", Cell Stress and Chaperones, vol. 19, no. 5, p. 695-703, 2014. https://doi.org/10.1007/s12192-014-0497-4
