Abstract
CYCLIN-dependent kinase 5 (Cdk5) was originally isolated through its structural homology to human Cdc21, a key regulator of cell-cycle progression2–6. In tissue samples from adult mice, Cdk5 protein is found at the highest level in brain, at an intermediate level in testis, and at low or undetectable levels in all other tissues, but brain is the only tissue that shows Cdk5 histone HI kinase activity7. No equivalent kinase activity has been found in tissue culture cell lines despite high levels of Cdk5. This raised the possibility that a Cdk5 regulatory subunit was responsible for the activation of Cdk5 in brain. Here we describe the cloning and characterization of a regulatory subunit for Cdk5 known as p35. p35 displays a neuronal cell-specific pattern of expression, it associates physically with Cdk5 in vivo and activates the Cdk5 kinase. p35 differs from the mammalian cyclins and thus represents a new type of regulatory subunit for cyclin-dependent kinase activity.
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References
Meyerson, M. et al. EMBO J. 11, 2909–2917 (1992).
Draetta, G. Trends biochem. Sci. 15, 378–383 (1990).
Murray, A. W. & Kirschner, M. W. Science 246, 614–621 (1989).
Nurse, P. Nature 344, 503–508 (1990).
Pines, J. & Hunter, T. New Biologist 2, 389–401 (1990).
Hunt, T. Curr. Opin. Cell Biol. 1, 268–274 (1989).
Tsai, L.-H., Takahashi, T., Caviness, V. S. & Harlow, E. Development 119, 1029–1040 (1993).
Sherr, C. J. Cell 73, 1059–1065 (1993).
Lew, J., Beaudette, K., Litwin, C. M. E. & Wang, J. H. J. biol. Chem. 267, 13383–13390 (1992).
Lew, J. et al. Nature 371, 423–426 (1994).
Hellmich, M. R., Pant, H. C., Wada, E. & Battey, J. F. Proc. natn. Acad. Sci. U.S.A. 89, 10867–10871 (1992).
van den Heuvel, S. & Harlow, E. Science 262, 2050–2054 (1993).
Yamamoto, M., Steinbusch, H. W. M. & Jessell, T. M. J. Cell Biol. 91, 142–152 (1981).
Herrmann, C., Su, L.-K. & Harlow, E. J. Virol. 65, 5848–5859 (1991).
Cleveland, D. W., Fischer, S. G., Kirschner, M. W. & Laemmli, U. K. J. biol. Chem. 252, 1102–1106 (1977).
Graham, F. L. & Van der Eb, A. J. Virology 52, 456–467 (1973).
Faha, B., Ewen, M., Tsai, L.-H., Livingston, D. & Harlow, E. Science 255, 87–90 (1992).
Ishiguro, K. et al. FEBS Lett. 342, 203–208 (1994).
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Tsai, LH., Delalle, I., Caviness, V. et al. p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5. Nature 371, 419–423 (1994). https://doi.org/10.1038/371419a0
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DOI: https://doi.org/10.1038/371419a0
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