Abstract
THE eukaryotic cell cycle is regulated by the sequential activation of cyclin-dependent kinases (CDKs)1. CDK activation is dependent on cyclin binding2–4 and phosphorylation of a conserved threonine (T161 in Cdc2)5–9 mediated by the CDK-activating kinase CAK9. A CDK-related kinase, MO15 (ref. 10), has been identified as the catalytic subunit of CAK (refs 11–13). Here we use a yeast two-hybrid screen to show that a new human cyclin (cyclin H) is a MO15-associated protein. Cyclin H is a major MO15 partner in vivo and enhances the kinase activity of MO15 towards Cdk2/cyclin A. These findings demonstrate that a cyclin/kinase complex can function as a regulator of other cyclin/kinase complexes, and suggest that cyclin/kinase cascades may exist.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Norbury, C. & Nurse, P. A. Rev. Biochem. 61, 441–470 (1992).
Draetta, G. et al. Cell 56, 829–838 (1989).
Pines, J. & Hunter, T. Cell 58, 833–846 (1989).
Solomon M. J., Glotzer, M., Lee, T. H., Philippe, M. & Kirschner, M. W. Cell 63, 1013–1024 (1990).
Gu, Y., Rosenblatt, J. & Morgan, D. O. EMBO J. 11, 3995–4005 (1992).
Desai, D., Gu, Y. & Morgan, D. O. Molec. Biol. Cell 3, 571–582 (1992).
Ducommun, B. et al. EMBO J. 10, 3311–3319 (1991).
Gould, K. L., Moreno, S., Owen, D. J., Sazer, S. & Nurse, P. EMBO J. 10, 3297–3309 (1991).
Solomon, M. J., Lee, T. & Kirschner, M. W. Molec. Biol. Cell 3, 13–27 (1992).
Shuttleworth, J., Godfrey, R. & Colman, A. EMBO J. 9, 3233–3240 (1990).
Fesquet, D. et al. EMBO J. 12, 3111–3121 (1993).
Poon, R. Y., Yamashita, K., Adamczewski, J. P., Hunt, T. & Shuttleworth, J. EMBO J. 12, 3123–3132 (1993).
Solomon, M. J., Harper, J. W. & Shuttleworth, J. EMBO J. 12, 3133–3142 (1993).
Fields, S. & Song, O. Nature 340, 245–246 (1989).
Gyuris, J., Golemis, E., Chertkov, H. & Brent, R. Cell 75, 791–803 (1993).
Molz, L. & Beach, D. EMBO J. 12, 1723–1732 (1993).
Valay, J. G., Simon, M. & Faye, G. J. molec. Biol. 234, 307–310 (1993).
Lew, D. J., Dulic, V. & Reed, S. I. Cell 66, 1197–1206 (1991).
Connell-Crowley, L., Solomon, M. J., Wei, N. & Harper, J. W. Molec. Biol. Cell 4, 79–92 (1993).
Tassan, J.-P., Schultz, S., Bartek, J. & Nigg, E. A. J. cell. Biol. (in the press).
Devereux, J., Haeberli, P. & Smithies, O. Nucleic Acids Res. 12, 387–395 (1984).
Levedakou, E. N. et al. Oncogene 9, 1977–1988 (1994).
Hinds, P. W. et al. Cell 70, 993–1006 (1992).
Harlow, E. & Lane, D. Antibodies: A Laboratory Manual (Cold Spring Harbor Laboratory, Cold Spring Harbor, 1988).
Ortiz, M. L., Calero, M., Patron, C. F., Castellanos, L. & Mendez, E. FEBS Lett. 296, 300–304 (1992).
Schägger, H. & von Jagow, G. Analyt. Biochem. 166, 368–379 (1987).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mäkelä, T., Tassan, JP., Nigg, E. et al. A cyclin associated with the CDK-activating kinase MO15. Nature 371, 254–257 (1994). https://doi.org/10.1038/371254a0
Issue date:
DOI: https://doi.org/10.1038/371254a0
This article is cited by
-
Erratum to: Controlling the response to DNA damage by the APC/C-Cdh1
Cellular and Molecular Life Sciences (2016)
-
Structures of the CDK12/CycK complex with AMP-PNP reveal a flexible C-terminal kinase extension important for ATP binding
Scientific Reports (2015)
-
Targeting transcription regulation in cancer with a covalent CDK7 inhibitor
Nature (2014)
-
TFIIH: when transcription met DNA repair
Nature Reviews Molecular Cell Biology (2012)
-
Temporal and Spatial Expression of Cyclin H in Rat Spinal Cord Injury
NeuroMolecular Medicine (2011)
