Cyclin H Explained

Cyclin-H is a protein that in humans is encoded by the CCNH gene.^{[1] [2]}

Function

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with CDK7 kinase and ring finger protein MAT1. The kinase complex is able to phosphorylate CDK2 and CDC2 kinases, thus functions as a CDK-activating kinase (CAK). This cyclin and its kinase partner are components of TFIIH, as well as RNA polymerase II protein complexes. They participate in two different transcriptional regulation processes, suggesting an important link between basal transcription control and the cell cycle machinery.

Interactions

Cyclin H has been shown to interact with P53,^[3] Cyclin-dependent kinase 7^{[4] [5] [6]} and MNAT1.^{[7] [8]}

References

Further reading

• Jeang KT . Tat, Tat-associated kinase, and transcription . Journal of Biomedical Science . 5 . 1 . 24–7 . 1998 . 9570510 . 10.1007/BF02253352 .
• Yankulov K, Bentley D . Transcriptional control: Tat cofactors and transcriptional elongation . Current Biology . 8 . 13 . R447–9 . Jun 1998 . 9651670 . 10.1016/S0960-9822(98)70289-1 . 15480646 . free . 1998CBio....8.R447Y .
• Shiekhattar R, Mermelstein F, Fisher RP, Drapkin R, Dynlacht B, Wessling HC, Morgan DO, Reinberg D . Cdk-activating kinase complex is a component of human transcription factor TFIIH . Nature . 374 . 6519 . 283–7 . Mar 1995 . 7533895 . 10.1038/374283a0 . 1995Natur.374..283S . 4282418 .
• Darbon JM, Devault A, Taviaux S, Fesquet D, Martinez AM, Galas S, Cavadore JC, Dorée M, Blanchard JM . Cloning, expression and subcellular localization of the human homolog of p40MO15 catalytic subunit of cdk-activating kinase . Oncogene . 9 . 11 . 3127–38 . November 1994 . 7936635 .
• Feaver WJ, Svejstrup JQ, Henry NL, Kornberg RD . Relationship of CDK-activating kinase and RNA polymerase II CTD kinase TFIIH/TFIIK . Cell . 79 . 6 . 1103–9 . December 1994 . 8001136 . 10.1016/0092-8674(94)90040-X . 205021029 .
• Fisher RP, Morgan DO . A novel cyclin associates with MO15/CDK7 to form the CDK-activating kinase . Cell . 78 . 4 . 713–24 . Aug 1994 . 8069918 . 10.1016/0092-8674(94)90535-5 . 2996948 .
• Mäkelä TP, Tassan JP, Nigg EA, Frutiger S, Hughes GJ, Weinberg RA . A cyclin associated with the CDK-activating kinase MO15 . Nature . 371 . 6494 . 254–7 . Sep 1994 . 8078587 . 10.1038/371254a0 . 1994Natur.371..254M . 4369898 .
• Perez JL, Shen X, Finkernagel S, Sciorra L, Jenkins NA, Gilbert DJ, Copeland NG, Wong TW . Identification and chromosomal mapping of a receptor tyrosine kinase with a putative phospholipid binding sequence in its ectodomain . Oncogene . 9 . 1 . 211–9 . Jan 1994 . 8302582 .
• Tassan JP, Jaquenoud M, Fry AM, Frutiger S, Hughes GJ, Nigg EA . In vitro assembly of a functional human CDK7-cyclin H complex requires MAT1, a novel 36 kDa RING finger protein . The EMBO Journal . 14 . 22 . 5608–17 . November 1995 . 8521818 . 394676 . 10.1002/j.1460-2075.1995.tb00248.x.
• Adamczewski JP, Rossignol M, Tassan JP, Nigg EA, Moncollin V, Egly JM . MAT1, cdk7 and cyclin H form a kinase complex which is UV light-sensitive upon association with TFIIH . The EMBO Journal . 15 . 8 . 1877–84 . Apr 1996 . 8617234 . 450106 . 10.1002/j.1460-2075.1996.tb00538.x.
• Blau J, Xiao H, McCracken S, O'Hare P, Greenblatt J, Bentley D . Three functional classes of transcriptional activation domain . Molecular and Cellular Biology . 16 . 5 . 2044–55 . May 1996 . 8628270 . 231191 . 10.1128/MCB.16.5.2044.
• Reardon JT, Ge H, Gibbs E, Sancar A, Hurwitz J, Pan ZQ . Isolation and characterization of two human transcription factor IIH (TFIIH)-related complexes: ERCC2/CAK and TFIIH . Proceedings of the National Academy of Sciences of the United States of America . 93 . 13 . 6482–7 . Jun 1996 . 8692841 . 39049 . 10.1073/pnas.93.13.6482 . 1996PNAS...93.6482R . free .
• Drapkin R, Le Roy G, Cho H, Akoulitchev S, Reinberg D . Human cyclin-dependent kinase-activating kinase exists in three distinct complexes . Proceedings of the National Academy of Sciences of the United States of America . 93 . 13 . 6488–93 . Jun 1996 . 8692842 . 39050 . 10.1073/pnas.93.13.6488 . 1996PNAS...93.6488D . free .
• Kim KK, Chamberlin HM, Morgan DO, Kim SH . Three-dimensional structure of human cyclin H, a positive regulator of the CDK-activating kinase . Nature Structural Biology . 3 . 10 . 849–55 . Oct 1996 . 8836101 . 10.1038/nsb1096-849 . 8880795 .
• Zhou Q, Sharp PA . Tat-SF1: cofactor for stimulation of transcriptional elongation by HIV-1 Tat . Science . 274 . 5287 . 605–10 . Oct 1996 . 8849451 . 10.1126/science.274.5287.605 . 1996Sci...274..605Z . 13266489 .
• Parada CA, Roeder RG . Enhanced processivity of RNA polymerase II triggered by Tat-induced phosphorylation of its carboxy-terminal domain . Nature . 384 . 6607 . 375–8 . Nov 1996 . 8934526 . 10.1038/384375a0 . 1996Natur.384..375P . 4278432 .
• Richard Gaynor . García-Martínez LF, Ivanov D, Gaynor RB . Association of Tat with purified HIV-1 and HIV-2 transcription preinitiation complexes . The Journal of Biological Chemistry . 272 . 11 . 6951–8 . Mar 1997 . 9054383 . 10.1074/jbc.272.11.6951 . free .
• Poterszman A, Andersen G, Busso D, Rossignol M, Egly JM, Thierry JC . Expression in Escherichia coli: purification and characterization of cyclin H, a subunit of the human general transcription/DNA repair factor TFIIH . Protein Expression and Purification . 9 . 2 . 153–8 . Mar 1997 . 9056480 . 10.1006/prep.1996.0693 .
• Marinoni JC, Roy R, Vermeulen W, Miniou P, Lutz Y, Weeda G, Seroz T, Gomez DM, Hoeijmakers JH, Egly JM . Cloning and characterization of p52, the fifth subunit of the core of the transcription/DNA repair factor TFIIH . The EMBO Journal . 16 . 5 . 1093–102 . Mar 1997 . 9118947 . 1169708 . 10.1093/emboj/16.5.1093 .
• Andersen G, Busso D, Poterszman A, Hwang JR, Wurtz JM, Ripp R, Thierry JC, Egly JM, Moras D . The structure of cyclin H: common mode of kinase activation and specific features . The EMBO Journal . 16 . 5 . 958–67 . Mar 1997 . 9118957 . 1169696 . 10.1093/emboj/16.5.958 .

Notes and References

1. Eki T, Okumura K, Abe M, Kagotani K, Taguchi H, Murakami Y, Pan ZQ, Hanaoka F . Mapping of the human genes encoding cyclin H (CCNH) and the CDK-activating kinase (CAK) assembly factor MAT1 (MNAT1) to chromosome bands 5q13.3-q14 and 14q23, respectively . Genomics . 47 . 1 . 115–20 . Jan 1998 . 9465303 . 10.1006/geno.1997.5053 .
2. Web site: Entrez Gene: CCNH cyclin H.
3. Schneider E, Montenarh M, Wagner P . Regulation of CAK kinase activity by p53 . Oncogene . 17 . 21 . 2733–41 . November 1998 . 9840937 . 10.1038/sj.onc.1202504 . 6281777 .
4. Mäkelä TP, Tassan JP, Nigg EA, Frutiger S, Hughes GJ, Weinberg RA . A cyclin associated with the CDK-activating kinase MO15 . Nature . 371 . 6494 . 254–7 . Sep 1994 . 8078587 . 10.1038/371254a0 . 1994Natur.371..254M . 4369898 .
5. Yee A, Nichols MA, Wu L, Hall FL, Kobayashi R, Xiong Y . Molecular cloning of CDK7-associated human MAT1, a cyclin-dependent kinase-activating kinase (CAK) assembly factor . Cancer Research . 55 . 24 . 6058–62 . December 1995 . 8521393 .
6. Garber ME, Mayall TP, Suess EM, Meisenhelder J, Thompson NE, Jones KA . CDK9 autophosphorylation regulates high-affinity binding of the human immunodeficiency virus type 1 tat-P-TEFb complex to TAR RNA . Molecular and Cellular Biology . 20 . 18 . 6958–69 . Sep 2000 . 10958691 . 88771 . 10.1128/MCB.20.18.6958-6969.2000 .
7. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .
8. Talukder AH, Mishra SK, Mandal M, Balasenthil S, Mehta S, Sahin AA, Barnes CJ, Kumar R . MTA1 interacts with MAT1, a cyclin-dependent kinase-activating kinase complex ring finger factor, and regulates estrogen receptor transactivation functions . The Journal of Biological Chemistry . 278 . 13 . 11676–85 . Mar 2003 . 12527756 . 10.1074/jbc.M209570200 . free .