Cyclin T1

Last updated
CCNT1
Protein CCNT1 PDB 2PK2.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases CCNT1 , CCNT, CYCT1, HIVE1, cyclin T1
External IDs OMIM: 143055 MGI: 1328363 HomoloGene: 947 GeneCards: CCNT1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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: 98.44 – 98.47 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

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 the following:

Related Research Articles

<span class="mw-page-title-main">P-TEFb</span>

The positive transcription elongation factor, P-TEFb, is a multiprotein complex that plays an essential role in the regulation of transcription by RNA polymerase II in eukaryotes. Immediately following initiation Pol II becomes trapped in promoter proximal paused positions on the majority of human genes. P-TEFb is a cyclin dependent kinase that can phosphorylate the DRB sensitivity inducing factor (DSIF) and negative elongation factor (NELF), as well as the carboxyl terminal domain of the large subunit of Pol II and this causes the transition into productive elongation leading to the synthesis of mRNAs. P-TEFb is regulated in part by a reversible association with the 7SK snRNP. Treatment of cells with the P-TEFb inhibitors DRB or flavopidirol leads to loss of mRNA production and ultimately cell death.

<span class="mw-page-title-main">7SK RNA</span> Small nuclear RNA found in metazoans

In molecular biology 7SK is an abundant small nuclear RNA found in metazoans. It plays a role in regulating transcription by controlling the positive transcription elongation factor P-TEFb. 7SK is found in a small nuclear ribonucleoprotein complex (snRNP) with a number of other proteins that regulate the stability and function of the complex.

<span class="mw-page-title-main">Cyclin-dependent kinase 9</span> Protein-coding gene in the species Homo sapiens

Cyclin-dependent kinase 9 or CDK9 is a cyclin-dependent kinase associated with P-TEFb.

<span class="mw-page-title-main">POLR2C</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerase II subunit RPB3 is an enzyme that in humans is encoded by the POLR2C gene.

<span class="mw-page-title-main">POLR2E</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerases I, II, and III subunit RPABC1 is a protein that in humans is encoded by the POLR2E gene.

<span class="mw-page-title-main">POLR2B</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerase II subunit RPB2 is an enzyme that in humans is encoded by the POLR2B gene.

<span class="mw-page-title-main">POLR2G</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerase II subunit RPB7 is an enzyme that in humans is encoded by the POLR2G gene.

<span class="mw-page-title-main">POLR2H</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerases I, II, and III subunit RPABC3 is a protein that in humans is encoded by the POLR2H gene.

<span class="mw-page-title-main">POLR2F</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerases I, II, and III subunit RPABC2 is a protein that in humans is encoded by the POLR2F gene.

<span class="mw-page-title-main">POLR2L</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerases I, II, and III subunit RPABC5 is a protein that in humans is encoded by the POLR2L gene.

<span class="mw-page-title-main">POLR2J</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerase II subunit RPB11-a is an enzyme that in humans is encoded by the POLR2J gene.

<span class="mw-page-title-main">RNA polymerase II subunit B4</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerase II subunit RPB4 is an enzyme that in humans is encoded by the POLR2D gene.

<span class="mw-page-title-main">POLR2I</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerase II subunit RPB9 is an enzyme that in humans is encoded by the POLR2I gene.

<span class="mw-page-title-main">SUPT5H</span> Protein-coding gene in the species Homo sapiens

Transcription elongation factor SPT5 is a protein that in humans is encoded by the SUPT5H gene.

<span class="mw-page-title-main">GTF2H4</span> Protein-coding gene in the species Homo sapiens

General transcription factor IIH subunit 4 is a protein that in humans is encoded by the GTF2H4 gene.

<span class="mw-page-title-main">HEXIM1</span> Protein-coding gene in the species Homo sapiens

Protein HEXIM1 is a protein that in humans is encoded by the HEXIM1 gene.

<span class="mw-page-title-main">Cyclin T2</span> Protein-coding gene in the species Homo sapiens

Cyclin-T2 is a protein that in humans is encoded by the CCNT2 gene.

<span class="mw-page-title-main">CTDSPL</span> Protein-coding gene in the species Homo sapiens

CTD small phosphatase-like protein is an enzyme that in humans is encoded by the CTDSPL gene.

<span class="mw-page-title-main">Cyclin K</span> Protein-coding gene in the species Homo sapiens

Cyclin-K is a protein that in humans is encoded by the CCNK gene.

Tat (HIV)

In molecular biology, Tat is a protein that is encoded for by the tat gene in HIV-1. Tat is a regulatory protein that drastically enhances the efficiency of viral transcription. Tat stands for "Trans-Activator of Transcription". The protein consists of between 86 and 101 amino acids depending on the subtype. Tat vastly increases the level of transcription of the HIV dsDNA. Before Tat is present, a small number of RNA transcripts will be made, which allow the Tat protein to be produced. Tat then binds to cellular factors and mediates their phosphorylation, resulting in increased transcription of all HIV genes, providing a positive feedback cycle. This in turn allows HIV to have an explosive response once a threshold amount of Tat is produced, a useful tool for defeating the body's response.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000129315 Ensembl, May 2017
  2. 1 2 3 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. 1 2 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. 1 2 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. 1 2 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. 1 2 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. S2CID   1338899.
  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. S2CID   21468451.
  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. S2CID   29519364.
  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