Cyclin T1 Explained

Cyclin-T1 is a protein that in humans is encoded by the CCNT1 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 that contribute to the temporal coordination of each mitotic event. This cyclin tightly associates with CDK9 kinase, and was found to be a major subunit of the transcription elongation factor p-TEFb. The kinase complex containing this cyclin and the elongation factor can interact with, and act as a cofactor of human immunodeficiency virus type 1 (HIV-1) Tat protein, and was shown to be both necessary and sufficient for full activation of viral transcription. This cyclin and its kinase partner were also found to be involved in the phosphorylation and regulation of the carboxy-terminal domain (CTD) of the largest RNA polymerase II subunit.^[3]

Interactions

Cyclin T1 has been shown to interact with the following:

• Aryl hydrocarbon receptor^[4]
• CDK9^{[5] [6] [7] [8] [9]}
• Granulin^[10]
• HEXIM1^[11]
• Myc^[12]
• NUFIP1^[13]
• Promyelocytic leukemia protein^[14]

Further reading

• Jeang KT . Tat, Tat-associated kinase, and transcription . J. Biomed. Sci. . 5 . 1 . 24–7 . 1998 . 9570510 . 10.1007/BF02253352 .
• Yankulov K, Bentley D . Transcriptional control: Tat cofactors and transcriptional elongation . Curr. Biol. . 8 . 13 . R447-9 . 1998 . 9651670 . 10.1016/S0960-9822(98)70289-1 . 15480646 . free . 1998CBio....8.R447Y .
• Romano G, Kasten M, De Falco G, Micheli P, Khalili K, Giordano A . Regulatory functions of Cdk9 and of cyclin T1 in HIV tat transactivation pathway gene expression . J. Cell. Biochem. . 75 . 3 . 357–68 . 1999 . 10536359 . 10.1002/(SICI)1097-4644(19991201)75:3<357::AID-JCB1>3.0.CO;2-K . 43685090 .
• Cunningham AL, Li S, Juarez J, Lynch G, Alali M, Naif H . The level of HIV infection of macrophages is determined by interaction of viral and host cell genotypes . J. Leukoc. Biol. . 68 . 3 . 311–7 . 2000 . 10.1189/jlb.68.3.311 . 10985245 . 38354228 .
• Marcello A, Zoppé M, Giacca M . Multiple modes of transcriptional regulation by the HIV-1 Tat transactivator . IUBMB Life . 51 . 3 . 175–81 . 2001 . 11547919 . 10.1080/152165401753544241 . 10931640 . free .
• Huigen MC, Kamp W, Nottet HS . Multiple effects of HIV-1 trans-activator protein on the pathogenesis of HIV-1 infection . Eur. J. Clin. Invest. . 34 . 1 . 57–66 . 2004 . 14984439 . 10.1111/j.1365-2362.2004.01282.x . 29713968 .
• Rice AP, Herrmann CH . Regulation of TAK/P-TEFb in CD4+ T lymphocytes and macrophages . Curr. HIV Res. . 1 . 4 . 395–404 . 2003 . 15049426 . 10.2174/1570162033485159 .
• Minghetti L, Visentin S, Patrizio M, Franchini L, Ajmone-Cat MA, Levi G . Multiple actions of the human immunodeficiency virus type-1 Tat protein on microglial cell functions . Neurochem. Res. . 29 . 5 . 965–78 . 2004 . 15139295 . 10.1023/B:NERE.0000021241.90133.89 . 25323034 .
• Kino T, Pavlakis GN . Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1 . DNA Cell Biol. . 23 . 4 . 193–205 . 2004 . 15142377 . 10.1089/104454904773819789 .
• Liou LY, Herrmann CH, Rice AP . HIV-1 infection and regulation of Tat function in macrophages . Int. J. Biochem. Cell Biol. . 36 . 9 . 1767–75 . 2004 . 15183343 . 10.1016/j.biocel.2004.02.018 .
• Pugliese A, Vidotto V, Beltramo T, Petrini S, Torre D . A review of HIV-1 Tat protein biological effects . Cell Biochem. Funct. . 23 . 4 . 223–7 . 2005 . 15473004 . 10.1002/cbf.1147 . 8408278 .
• Bannwarth S, Gatignol A . HIV-1 TAR RNA: the target of molecular interactions between the virus and its host . Curr. HIV Res. . 3 . 1 . 61–71 . 2005 . 15638724 . 10.2174/1570162052772924 .
• Gibellini D, Vitone F, Schiavone P, Re MC . HIV-1 tat protein and cell proliferation and survival: a brief review . New Microbiol. . 28 . 2 . 95–109 . 2005 . 16035254 .
• Peruzzi F . The multiple functions of HIV-1 Tat: proliferation versus apoptosis . Front. Biosci. . 11 . 708–717 . 2006 . 16146763 . 10.2741/1829 . 12438136 . https://web.archive.org/web/20190224064144/http://pdfs.semanticscholar.org/51ff/1d7d11a9a0d32cfe24472acd508707bd43f1.pdf . dead . 2019-02-24 .

Notes and References

1. Wei P, Garber ME, Fang SM, Fischer WH, Jones KA . A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA . Cell . 92 . 4 . 451–62 . March 1998 . 9491887 . 10.1016/S0092-8674(00)80939-3 . 16395032 . free .
2. Peng J, Zhu Y, Milton JT, Price DH . Identification of multiple cyclin subunits of human P-TEFb . Genes Dev. . 12 . 5 . 755–62 . April 1998 . 9499409 . 316581 . 10.1101/gad.12.5.755 .
3. Web site: Entrez Gene: CCNT1 cyclin T1.
4. Tian Y, Ke S, Chen M, Sheng T . Interactions between the aryl hydrocarbon receptor and P-TEFb. Sequential recruitment of transcription factors and differential phosphorylation of C-terminal domain of RNA polymerase II at cyp1a1 promoter . J. Biol. Chem. . 278 . 45 . 44041–8 . November 2003 . 12917420 . 10.1074/jbc.M306443200 . free .
5. Young TM, Wang Q, Pe'ery T, Mathews MB . The human I-mfa domain-containing protein, HIC, interacts with cyclin T1 and modulates P-TEFb-dependent transcription . Mol. Cell. Biol. . 23 . 18 . 6373–84 . September 2003 . 12944466 . 193714 . 10.1128/mcb.23.18.6373-6384.2003.
6. Kiernan RE, Emiliani S, Nakayama K, Castro A, Labbé JC, Lorca T, Nakayama Ki K, Benkirane M . Interaction between cyclin T1 and SCF(SKP2) targets CDK9 for ubiquitination and degradation by the proteasome . Mol. Cell. Biol. . 21 . 23 . 7956–70 . December 2001 . 11689688 . 99964 . 10.1128/MCB.21.23.7956-7970.2001 .
7. De Falco G, Bagella L, Claudio PP, De Luca A, Fu Y, Calabretta B, Sala A, Giordano A . Physical interaction between CDK9 and B-Myb results in suppression of B-Myb gene autoregulation . Oncogene . 19 . 3 . 373–9 . January 2000 . 10656684 . 10.1038/sj.onc.1203305 . 21468451 .
8. Fu TJ, Peng J, Lee G, Price DH, Flores O . Cyclin K functions as a CDK9 regulatory subunit and participates in RNA polymerase II transcription . J. Biol. Chem. . 274 . 49 . 34527–30 . December 1999 . 10574912 . 10.1074/jbc.274.49.34527. free .
9. 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 . Mol. Cell. Biol. . 20 . 18 . 6958–69 . September 2000 . 10958691 . 88771 . 10.1128/mcb.20.18.6958-6969.2000.
10. Hoque M, Young TM, Lee CG, Serrero G, Mathews MB, Pe'ery T . The growth factor granulin interacts with cyclin T1 and modulates P-TEFb-dependent transcription . Mol. Cell. Biol. . 23 . 5 . 1688–702 . March 2003 . 12588988 . 151712 . 10.1128/mcb.23.5.1688-1702.2003.
11. Michels AA, Nguyen VT, Fraldi A, Labas V, Edwards M, Bonnet F, Lania L, Bensaude O . MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner . Mol. Cell. Biol. . 23 . 14 . 4859–69 . July 2003 . 12832472 . 162212 . 10.1128/mcb.23.14.4859-4869.2003.
12. Kanazawa S, Soucek L, Evan G, Okamoto T, Peterlin BM . c-Myc recruits P-TEFb for transcription, cellular proliferation and apoptosis . Oncogene . 22 . 36 . 5707–11 . August 2003 . 12944920 . 10.1038/sj.onc.1206800 . 29519364 .
13. Cabart P, Chew HK, Murphy S . BRCA1 cooperates with NUFIP and P-TEFb to activate transcription by RNA polymerase II . Oncogene . 23 . 31 . 5316–29 . July 2004 . 15107825 . 10.1038/sj.onc.1207684 . 1338899 .
14. Marcello A, Ferrari A, Pellegrini V, Pegoraro G, Lusic M, Beltram F, Giacca M . Recruitment of human cyclin T1 to nuclear bodies through direct interaction with the PML protein . EMBO J. . 22 . 9 . 2156–66 . May 2003 . 12727882 . 156077 . 10.1093/emboj/cdg205 .