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Gene Review

CCNH  -  cyclin H

Homo sapiens

Synonyms: CAK, CycH, Cyclin-H, MO15-associated protein, p34, ...
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Disease relevance of CCNH


High impact information on CCNH

  • In addition, mimicking cdk8 phosphorylation of cyclin H in vivo has a dominant-negative effect on cell growth [6].
  • Here we use a yeast two-hybrid screen to show that a new human cyclin (cyclin H) is a MO15-associated protein [7].
  • Recent results on the structures of two cyclins, cyclin A and cyclin H, and two transcription factor mediator proteins, TFIIB and the A pocket region of the retinoblastoma tumour suppressor protein (Rb), show that they share domains with a strikingly similar alpha-helical topology, despite remote sequence identity [8].
  • The subunits of this enzyme have been identified recently as p40MO15, the catalytic subunit, and cyclin H, a regulatory subunit [9].
  • The specificity of the cyclin H molecule is provided mainly by two long helices which extend the cyclin fold at its N- and C-termini and pack together against the first repeat on the side opposite to the kinase [10].

Chemical compound and disease context of CCNH


Biological context of CCNH


Anatomical context of CCNH

  • The human MAT1 gene expresses a single 1.6-kb transcript, the steady-state level of which, like CDK7 and cyclin H, varies significantly in different cell lines and in different terminally differentiated tissues [17].
  • Finally, both cyclin H and cdk7 did not colocalize with P80 coilin after disruption of the coiled body, indicating that these proteins are specifically targeted to the small nuclear ribonucleoprotein-containing domain [18].
  • The nuclear localization of both the MO15 gene product and CAK activity may imply that cdks activation primarily occurs in the cell nucleus [16].
  • However, in peripheral blood lymphocytes (PBL) from HIV-infected patients, cyclin B and p34 cdc kinase show premature expression during the cell cycle [4].
  • Unscheduled cyclin B expression and p34 cdc2 activation in T lymphocytes from HIV-infected patients [4].

Associations of CCNH with chemical compounds


Physical interactions of CCNH


Other interactions of CCNH


Analytical, diagnostic and therapeutic context of CCNH


  1. Chromosomal imbalances associated with response to chemotherapy and cytotoxic cytokines in human malignant glioma cell lines. Weber, R.G., Rieger, J., Naumann, U., Lichter, P., Weller, M. Int. J. Cancer (2001) [Pubmed]
  2. Expression in Escherichia coli: purification and characterization of cyclin H, a subunit of the human general transcription/DNA repair factor TFIIH. Poterszman, A., Andersen, G., Busso, D., Rossignol, M., Egly, J.M., Thierry, J.C. Protein Expr. Purif. (1997) [Pubmed]
  3. Borrelia burgdorferi P35 and P37 proteins, expressed in vivo, elicit protective immunity. Fikrig, E., Barthold, S.W., Sun, W., Feng, W., Telford, S.R., Flavell, R.A. Immunity (1997) [Pubmed]
  4. Unscheduled cyclin B expression and p34 cdc2 activation in T lymphocytes from HIV-infected patients. Piedimonte, G., Corsi, D., Paiardini, M., Cannavò, G., Ientile, R., Picerno, I., Montroni, M., Silvestri, G., Magnani, M. AIDS (1999) [Pubmed]
  5. Differential expression of Borrelia burgdorferi genes during erythema migrans and Lyme arthritis. Fikrig, E., Feng, W., Aversa, J., Schoen, R.T., Flavell, R.A. J. Infect. Dis. (1998) [Pubmed]
  6. TFIIH is negatively regulated by cdk8-containing mediator complexes. Akoulitchev, S., Chuikov, S., Reinberg, D. Nature (2000) [Pubmed]
  7. A cyclin associated with the CDK-activating kinase MO15. Mäkelä, T.P., Tassan, J.P., Nigg, E.A., Frutiger, S., Hughes, G.J., Weinberg, R.A. Nature (1994) [Pubmed]
  8. The cyclin box fold: protein recognition in cell-cycle and transcription control. Noble, M.E., Endicott, J.A., Brown, N.R., Johnson, L.N. Trends Biochem. Sci. (1997) [Pubmed]
  9. The function(s) of CAK, the p34cdc2-activating kinase. Solomon, M.J. Trends Biochem. Sci. (1994) [Pubmed]
  10. The structure of cyclin H: common mode of kinase activation and specific features. Andersen, G., Busso, D., Poterszman, A., Hwang, J.R., Wurtz, J.M., Ripp, R., Thierry, J.C., Egly, J.M., Moras, D. EMBO J. (1997) [Pubmed]
  11. Elimination of cell-cycle regulators during caspase-3-dependent apoptosis caused by an immunosuppressant, FTY720. Lee, Y.S., Nakajima, H., Tsuruga, M., Magae, J. Biosci. Biotechnol. Biochem. (2003) [Pubmed]
  12. Identification of a cdk-activating kinase in fission yeast. Buck, V., Russell, P., Millar, J.B. EMBO J. (1995) [Pubmed]
  13. Lower cyclin H and cyclin-dependent kinase-activating kinase activity in cell cycle arrest induced by lack of adhesion to substratum. Solorzano, L., Rieber, M.S., Rieber, M. Cancer Res. (2000) [Pubmed]
  14. In vitro assembly of a functional human CDK7-cyclin H complex requires MAT1, a novel 36 kDa RING finger protein. Tassan, J.P., Jaquenoud, M., Fry, A.M., Frutiger, S., Hughes, G.J., Nigg, E.A. EMBO J. (1995) [Pubmed]
  15. Cyclin H binding to the RARalpha activation function (AF)-2 domain directs phosphorylation of the AF-1 domain by cyclin-dependent kinase 7. Bour, G., Gaillard, E., Bruck, N., Lalevée, S., Plassat, J.L., Busso, D., Samama, J.P., Rochette-Egly, C. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  16. Cloning, expression and subcellular localization of the human homolog of p40MO15 catalytic subunit of cdk-activating kinase. Darbon, J.M., Devault, A., Taviaux, S., Fesquet, D., Martinez, A.M., Galas, S., Cavadore, J.C., Dorée, M., Blanchard, J.M. Oncogene (1994) [Pubmed]
  17. Molecular cloning of CDK7-associated human MAT1, a cyclin-dependent kinase-activating kinase (CAK) assembly factor. Yee, A., Nichols, M.A., Wu, L., Hall, F.L., Kobayashi, R., Xiong, Y. Cancer Res. (1995) [Pubmed]
  18. The cdk7-cyclin H-MAT1 complex associated with TFIIH is localized in coiled bodies. Jordan, P., Cunha, C., Carmo-Fonseca, M. Mol. Biol. Cell (1997) [Pubmed]
  19. Reciprocal activation by cyclin-dependent kinases 2 and 7 is directed by substrate specificity determinants outside the T loop. Garrett, S., Barton, W.A., Knights, R., Jin, P., Morgan, D.O., Fisher, R.P. Mol. Cell. Biol. (2001) [Pubmed]
  20. Phosphorylation by PKA potentiates retinoic acid receptor alpha activity by means of increasing interaction with and phosphorylation by cyclin H/cdk7. Gaillard, E., Bruck, N., Brelivet, Y., Bour, G., Lalevée, S., Bauer, A., Poch, O., Moras, D., Rochette-Egly, C. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  21. Platelet-agglutinating protein P37 from a thrombotic thrombocytopenic purpura plasma forms a complex with human immunoglobulin G. Siddiqui, F.A., Lian, E.C. Blood (1988) [Pubmed]
  22. Structural organization of the gene for human CD36 glycoprotein. Armesilla, A.L., Vega, M.A. J. Biol. Chem. (1994) [Pubmed]
  23. A heterocomplex formed by the calcium-binding proteins MRP8 (S100A8) and MRP14 (S100A9) binds unsaturated fatty acids with high affinity. Siegenthaler, G., Roulin, K., Chatellard-Gruaz, D., Hotz, R., Saurat, J.H., Hellman, U., Hagens, G. J. Biol. Chem. (1997) [Pubmed]
  24. Cyclin H is targeted to the nucleus by C-terminal nuclear localization sequences. Krempler, A., Kartarius, S., Günther, J., Montenarh, M. Cell. Mol. Life Sci. (2005) [Pubmed]
  25. Specific changes in the posttranslational regulation of nucleolin in lymphocytes from patients infected with human immunodeficiency virus. Galati, D., Paiardini, M., Cervasi, B., Albrecht, H., Bocchino, M., Costantini, A., Montroni, M., Magnani, M., Piedimonte, G., Silvestri, G. J. Infect. Dis. (2003) [Pubmed]
  26. Structure of yellow lupine genes coding for mitotic cyclins. Jeleńska, J., Zaborowska, Z., Legocki, A.B. Acta Biochim. Pol. (1999) [Pubmed]
  27. A novel candidate oncogene, MCT-1, is involved in cell cycle progression. Prosniak, M., Dierov, J., Okami, K., Tilton, B., Jameson, B., Sawaya, B.E., Gartenhaus, R.B. Cancer Res. (1998) [Pubmed]
  28. Schizosaccharomyces pombe Mop1-Mcs2 is related to mammalian CAK. Damagnez, V., Mäkelä, T.P., Cottarel, G. EMBO J. (1995) [Pubmed]
  29. p53 is phosphorylated by CDK7-cyclin H in a p36MAT1-dependent manner. Ko, L.J., Shieh, S.Y., Chen, X., Jayaraman, L., Tamai, K., Taya, Y., Prives, C., Pan, Z.Q. Mol. Cell. Biol. (1997) [Pubmed]
  30. CAK-Cyclin-dependent Activating Kinase: a key kinase in cell cycle control and a target for drugs? Lolli, G., Johnson, L.N. Cell Cycle (2005) [Pubmed]
  31. Cyclin H is a new binding partner for protein kinase CK2. Faust, M., Kartarius, S., Schwindling, S.L., Montenarh, M. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  32. Morphological and molecular course of mitochondrial pathology in cultured human cells exposed long-term to Zidovudine. Divi, R.L., Haverkos, K.J., Humsi, J.A., Shockley, M.E., Thamire, C., Nagashima, K., Olivero, O.A., Poirier, M.C. Environ. Mol. Mutagen. (2007) [Pubmed]
  33. Cyclin-dependent kinase activating kinase/Cdk7 co-localizes with PKC-iota in human glioma cells. Bicaku, E., Patel, R., Acevedo-Duncan, M. Tissue & cell. (2005) [Pubmed]
  34. Human glioma PKC-iota and PKC-betaII phosphorylate cyclin-dependent kinase activating kinase during the cell cycle. Acevedo-Duncan, M., Patel, R., Whelan, S., Bicaku, E. Cell Prolif. (2002) [Pubmed]
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