Cyclin T1

Cyclin-T1 is a protein that in humans is encoded by the CCNT1 gene.[5][6]

CCNT1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2PK2, 3BLH, 3BLQ, 3BLR, 3LQ5, 3MI9, 3MIA, 3MY1, 3TN8, 3TNH, 3TNI, 4BCF, 4BCG, 4BCH, 4BCI, 4BCJ, 4EC8, 4EC9, 4IMY, 4OGR, 4OR5
Identifiers
Aliases	CCNT1, CCNT, CYCT1, HIVE1, cyclin T1
External IDs	OMIM: 143055 MGI: 1328363 HomoloGene: 947 GeneCards: CCNT1
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q13.11-q13.12 Start 48,688,458 bp[1] End 48,716,998 bp[1]
Gene location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15|15 F1 Start 98,538,689 bp[2] End 98,570,923 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • DNA binding • snRNA binding • chromatin binding • 7SK snRNA binding • cyclin-dependent protein serine/threonine kinase regulator activity • GO:0001948 protein binding • RNA polymerase binding • transcription factor binding • protein serine/threonine kinase activity • protein kinase binding • GO:0016534 cyclin-dependent protein serine/threonine kinase activator activity Cellular component • nucleoplasm • nucleolus • cyclin/CDK positive transcription elongation factor complex • cell nucleus • cyclin-dependent protein kinase holoenzyme complex Biological process • regulation of cyclin-dependent protein serine/threonine kinase activity • negative regulation of mRNA polyadenylation • regulation of transcription, DNA-templated • transcription elongation from RNA polymerase II promoter • transcription from RNA polymerase II promoter • cell division • protein phosphorylation • positive regulation of phosphorylation of RNA polymerase II C-terminal domain • positive regulation of cyclin-dependent protein serine/threonine kinase activity • positive regulation of viral transcription • cell cycle • positive regulation of transcription from RNA polymerase II promoter • GO:0022415 viral process • transcription, DNA-templated • snRNA transcription from RNA polymerase II promoter • regulation of transcription from RNA polymerase II promoter • positive regulation of DNA-templated transcription, elongation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	904	12455
Ensembl	ENSG00000129315	ENSMUSG00000011960
UniProt	O60563	Q9QWV9
RefSeq (mRNA)	NM_001240 NM_001277842	NM_009833 NM_001368702
RefSeq (protein)	NP_001231 NP_001264771	NP_033963 NP_001355631
Location (UCSC)	Chr 12: 48.69 – 48.72 Mb	Chr 15: 98.54 – 98.57 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[7]

Interactions

Cyclin T1 has been shown to interact with:

• Aryl hydrocarbon receptor,[8]
• CDK9,[6][9][10][11][12][13][14][15][16]
• Granulin,[10]
• HEXIM1,[9]
• Myc,[17]
• NUFIP1,[11] and
• Promyelocytic leukemia protein.[18]

References

1. GRCh38: Ensembl release 89: ENSG00000129315 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000011960 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Wei P, Garber ME, Fang SM, Fischer WH, Jones KA (March 1998). "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. doi:10.1016/S0092-8674(00)80939-3. PMID 9491887. S2CID 16395032.
6. Peng J, Zhu Y, Milton JT, Price DH (April 1998). "Identification of multiple cyclin subunits of human P-TEFb". Genes Dev. 12 (5): 755–62. doi:10.1101/gad.12.5.755. PMC 316581. PMID 9499409.
7. "Entrez Gene: CCNT1 cyclin T1".
8. Tian Y, Ke S, Chen M, Sheng T (November 2003). "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. doi:10.1074/jbc.M306443200. PMID 12917420.
9. Michels AA, Nguyen VT, Fraldi A, Labas V, Edwards M, Bonnet F, Lania L, Bensaude O (July 2003). "MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner". Mol. Cell. Biol. 23 (14): 4859–69. doi:10.1128/mcb.23.14.4859-4869.2003. PMC 162212. PMID 12832472.
10. Hoque M, Young TM, Lee CG, Serrero G, Mathews MB, Pe'ery T (March 2003). "The growth factor granulin interacts with cyclin T1 and modulates P-TEFb-dependent transcription". Mol. Cell. Biol. 23 (5): 1688–702. doi:10.1128/mcb.23.5.1688-1702.2003. PMC 151712. PMID 12588988.
11. Cabart P, Chew HK, Murphy S (July 2004). "BRCA1 cooperates with NUFIP and P-TEFb to activate transcription by RNA polymerase II". Oncogene. 23 (31): 5316–29. doi:10.1038/sj.onc.1207684. PMID 15107825.
12. Young TM, Wang Q, Pe'ery T, Mathews MB (September 2003). "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. doi:10.1128/mcb.23.18.6373-6384.2003. PMC 193714. PMID 12944466.
13. Kiernan RE, Emiliani S, Nakayama K, Castro A, Labbé JC, Lorca T, Nakayama Ki K, Benkirane M (December 2001). "Interaction between cyclin T1 and SCF(SKP2) targets CDK9 for ubiquitination and degradation by the proteasome". Mol. Cell. Biol. 21 (23): 7956–70. doi:10.1128/MCB.21.23.7956-7970.2001. PMC 99964. PMID 11689688.
14. De Falco G, Bagella L, Claudio PP, De Luca A, Fu Y, Calabretta B, Sala A, Giordano A (January 2000). "Physical interaction between CDK9 and B-Myb results in suppression of B-Myb gene autoregulation". Oncogene. 19 (3): 373–9. doi:10.1038/sj.onc.1203305. PMID 10656684.
15. Fu TJ, Peng J, Lee G, Price DH, Flores O (December 1999). "Cyclin K functions as a CDK9 regulatory subunit and participates in RNA polymerase II transcription". J. Biol. Chem. 274 (49): 34527–30. doi:10.1074/jbc.274.49.34527. PMID 10574912.
16. Garber ME, Mayall TP, Suess EM, Meisenhelder J, Thompson NE, Jones KA (September 2000). "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. doi:10.1128/mcb.20.18.6958-6969.2000. PMC 88771. PMID 10958691.
17. Kanazawa S, Soucek L, Evan G, Okamoto T, Peterlin BM (August 2003). "c-Myc recruits P-TEFb for transcription, cellular proliferation and apoptosis". Oncogene. 22 (36): 5707–11. doi:10.1038/sj.onc.1206800. PMID 12944920.
18. Marcello A, Ferrari A, Pellegrini V, Pegoraro G, Lusic M, Beltram F, Giacca M (May 2003). "Recruitment of human cyclin T1 to nuclear bodies through direct interaction with the PML protein". EMBO J. 22 (9): 2156–66. doi:10.1093/emboj/cdg205. PMC 156077. PMID 12727882.

Further reading

• Jeang KT (1998). "Tat, Tat-associated kinase, and transcription". J. Biomed. Sci. 5 (1): 24–7. doi:10.1007/BF02253352. PMID 9570510.
• Yankulov K, Bentley D (1998). "Transcriptional control: Tat cofactors and transcriptional elongation". Curr. Biol. 8 (13): R447-9. doi:10.1016/S0960-9822(98)70289-1. PMID 9651670. S2CID 15480646.
• Romano G, Kasten M, De Falco G, Micheli P, Khalili K, Giordano A (1999). "Regulatory functions of Cdk9 and of cyclin T1 in HIV tat transactivation pathway gene expression". J. Cell. Biochem. 75 (3): 357–68. doi:10.1002/(SICI)1097-4644(19991201)75:3<357::AID-JCB1>3.0.CO;2-K. PMID 10536359.
• Cunningham AL, Li S, Juarez J, Lynch G, Alali M, Naif H (2000). "The level of HIV infection of macrophages is determined by interaction of viral and host cell genotypes". J. Leukoc. Biol. 68 (3): 311–7. PMID 10985245.
• Marcello A, Zoppé M, Giacca M (2001). "Multiple modes of transcriptional regulation by the HIV-1 Tat transactivator". IUBMB Life. 51 (3): 175–81. doi:10.1080/152165401753544241. PMID 11547919. S2CID 10931640.
• Huigen MC, Kamp W, Nottet HS (2004). "Multiple effects of HIV-1 trans-activator protein on the pathogenesis of HIV-1 infection". Eur. J. Clin. Invest. 34 (1): 57–66. doi:10.1111/j.1365-2362.2004.01282.x. PMID 14984439. S2CID 29713968.
• Rice AP, Herrmann CH (2003). "Regulation of TAK/P-TEFb in CD4+ T lymphocytes and macrophages". Curr. HIV Res. 1 (4): 395–404. doi:10.2174/1570162033485159. PMID 15049426.
• Minghetti L, Visentin S, Patrizio M, Franchini L, Ajmone-Cat MA, Levi G (2004). "Multiple actions of the human immunodeficiency virus type-1 Tat protein on microglial cell functions". Neurochem. Res. 29 (5): 965–78. doi:10.1023/B:NERE.0000021241.90133.89. PMID 15139295. S2CID 25323034.
• Kino T, Pavlakis GN (2004). "Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1". DNA Cell Biol. 23 (4): 193–205. doi:10.1089/104454904773819789. PMID 15142377.
• Liou LY, Herrmann CH, Rice AP (2004). "HIV-1 infection and regulation of Tat function in macrophages". Int. J. Biochem. Cell Biol. 36 (9): 1767–75. doi:10.1016/j.biocel.2004.02.018. PMID 15183343.
• Pugliese A, Vidotto V, Beltramo T, Petrini S, Torre D (2005). "A review of HIV-1 Tat protein biological effects". Cell Biochem. Funct. 23 (4): 223–7. doi:10.1002/cbf.1147. PMID 15473004. S2CID 8408278.
• Bannwarth S, Gatignol A (2005). "HIV-1 TAR RNA: the target of molecular interactions between the virus and its host". Curr. HIV Res. 3 (1): 61–71. doi:10.2174/1570162052772924. PMID 15638724.
• Gibellini D, Vitone F, Schiavone P, Re MC (2005). "HIV-1 tat protein and cell proliferation and survival: a brief review". New Microbiol. 28 (2): 95–109. PMID 16035254.
• Peruzzi F (2006). "The multiple functions of HIV-1 Tat: proliferation versus apoptosis" (PDF). Front. Biosci. 11: 708–717. doi:10.2741/1829. PMID 16146763. S2CID 12438136.