Nature 374, 280 - 282 (16 March 2002); doi:10.1038/374280a0

Association of Cdk-activating kinase subunits with transcription factor TFIIH

Hiroaki Serizawa, Tomi P. Mäkelä, Joan Weliky Conaway^*, Ronald C. Conaway^*, Robert A. Weinberg & Richard A. Young

Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142 and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
^*Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA

THE RNA polymerase II large subunit contains an essential carboxy-terminal domain (CTD) believed to be involved in the response to regulators during transcription initiation^1–10. The CTD is phosphorylated on a portion of RNA polymerase II molecules in in vivo ^11,12 and it can be phosphorylated by the general transcription factor TFIIH in vitro ^13–15. A highly purified TFIIH from rat liver has been described¹⁶; this, like human and yeast TFIIH, contains associated CTD kinase and helicase activities^13–18. We report here that two polypeptides of the purified mammalian TFIIH are the MO15/Cdk7 kinase and cyclin H subunits of the Cdk-activating kinase Cak^19–21, previously identified as a positive regulator of Cdc2 and Cdk2. TFIIH and Cak preparations are each capable of phosphorylating recombinant CTD and recombi-nant Cdk2 proteins. The presence of Cak in TFIIH indicates that Cak may have roles in transcriptional regulation and in cell-cycle control.

References

1.	Corden, J. L. Trends biochem. Sci. 15, 383−387 (1990). | Article | PubMed | ChemPort |
2.	Young, R. A. A. Rev. Biochem. 60, 689−715 (1991). | Article | ChemPort |
3.	Dahmus, M. E. & Dynan, W. S. in Transcriptional Regulation 109−128 (Cold Spring Harbor Laboratory Press, New York, 1992).
4.	Allison, L. A. & Ingles, C. J. Proc. natn. Acad. Sci. U.S.A. 86, 2794−2798 (1989). | ChemPort |
5.	Scafe, C. et al. Nature 347, 491−494 (1990). | Article | PubMed | ISI | ChemPort |
6.	Peterson, C. L., Kruger, W. & Herskowitz, I. Cell 64, 1135−1143 (1991). | Article | PubMed | ISI | ChemPort |
7.	Koleske, A. J., Buratowski, S., Nonet, M. & Young, R. A. Cell 69, 883−894 (1992). | Article | PubMed | ISI | ChemPort |
8.	Thompson, C. M., Koleske, A. J., Chao, D. M. & Young, R. A. Cell 73, 1361−1375 (1993). | Article | PubMed | ISI | ChemPort |
9.	Koleske, A. J. & Young, R. A. Nature 368, 466−469 (1994). | Article | PubMed | ISI | ChemPort |
10.	Kim, Y.-J., Bjorklund, S., Li, Y., Sayre, M. H. & Kornberg, R. D. Cell 77, 599−609 (1994). | Article | PubMed | ISI | ChemPort |
11.	Cadena, D. L. & Dahmus, M. E. J. biol. Chem. 262, 12468−12474 (1987). | PubMed | ISI | ChemPort |
12.	Kolodziej, P. A., Woychik, N., Liao, S.-M. & Young, R. A. Molec. cell. Biol. 10, 1915−1929 (1990). | PubMed | ChemPort |
13.	Feaver, W. J., Gileadi, O., Li, Y. & Kornberg, R. Cell 67, 1223−1330 (1991). | Article | PubMed | ISI | ChemPort |
14.	Serizawa, H., Conaway, R. C. & Conaway, J. W. Proc. natn. Acad. Sci. U.S.A. 89, 7476−7480 (1992). | ChemPort |
15.	Lu, H., Zawel, L., Fischer, L., Egly, J. M. & Reinberg, D. Nature 358, 641−645 (1992). | Article | PubMed | ISI | ChemPort |
16.	Conaway, R. C. & Conaway, J. W. Proc. natn. Acad. Sci. U.S.A. 86, 7356−7360 (1989). | ChemPort |
17.	Serizawa, H., Conaway, R. C. & Conaway, J. W. J. biol. Chem. 268, 17300−17308 (1993). | PubMed | ISI | ChemPort |
18.	Schaeffer, L. et al. Science 260, 58−63 (1993). | PubMed | ChemPort |
19.	Solomon, M. J., Lee, T. & Kirschner, M. W. Molec. Biol. Cell 3, 13−27 (1992). | PubMed | ChemPort |
20.	Fisher, R. P. & Morgan, D. O. Cell 78, 713−724 (1994). | Article | PubMed | ISI | ChemPort |
21.	Mäkelä, T. P. et al. Nature 371, 254−256 (1994). | Article | PubMed | ISI | ChemPort |
22.	Gu, Y., Rosenblatt, J. & Morgan, D. O. EMBO J. 11, 3995−4005 (1992). | PubMed | ISI | ChemPort |
23.	O'Brien, T., Hardin, S., Greenleaf, A. & Lis, J. T. Nature 370, 75−77 (1994). | Article | PubMed | ChemPort |
24.	Matsuoka, M., Kato, J.-Y., Fisher, R. P., Morgan, D. & Sherr, C. J. Molec. cell Biol. 14, 7265−7275 (1994). | PubMed | ChemPort |
25.	Buratowski, S. & Sharp, P. Molec. cell. Biol. 10, 5562−5564 (1990). | PubMed | ChemPort |
26.	Li, Y. & Kornberg, R. D. Proc. natn. Acad. Sci. U.S.A. 91, 2362−2366 (1994). | ChemPort |
27.	Serizawa, H., Conaway, J. W. & Conaway, R. C. Nature 363, 371−374 (1993). | Article | PubMed | ISI | ChemPort |
28.	Conaway, R. C. & Conaway, J. W. J. biol. Chem. 263, 2962−2968 (1988). | PubMed | ChemPort |
29.	Harlow, E. & Lane, D. Antibodies: A Laboratory Manual (Cold Spring Harbor Laboratory Press, New York, 1989).
30.	van der Geer, P., Luo, K., Sefton, B. M. & Hunter, T. in Protein Phosphorylation (ed. Hardie, D. G.) 31−59 (IRL, Oxford, 1993). | ChemPort |
31.	Roy, R. et al. Cell 79, 1093−1101 (1994). | Article | PubMed | ISI | ChemPort |
32.	Feaver, W. J., Svejstrup, J. Q., Henry, N. L. & Kornberg, R. D. Cell 79, 1103−1109 (1994). | Article | PubMed | ISI | ChemPort |