Cyclin

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Contents

Function

Cyclin (CYC) activates CYC-dependent kinase (CDK) thus acting in the control of the cell cycle. The CYC name derives from the fact that different CYCs are expressed during different phases of the cell cycle. Among the CYCs:

  • CYCA is active in the S phase
  • CYCA2 regulates DNA replication and mitotic entry.[1]
  • CYCB1 is essential for the control of the cell cycle at the G2/M (mitosis) transition.
  • CYCC is active in the G0/G1 phase transition[2].
  • CYCCCL1 controls the phosphorylation of RNA polymerase II largest subunit and mRNA transcription [3]
  • CYCD regulates the transition from G1 to S.[4]
  • CYCE and its CDK partner are key regulators of DNA synthesis and of mitosis.[5]
  • CYCF is the substrate recognition component of the Skp1-Cul1-F-box E3 ubiquitin ligase complex[6]
  • CYCH is highly expressed in ovarian cancer[7]
  • CYCK and its CDK12 partner regulate the expression of DNA-damage response genes and thus protect cells from genomic instability.[8]
  • CYCT and its CDK9 partner regulate gene expression.[9]
  • Viral CYC could be involved in oncogenic events associated with the cyclin-encoding viruses.[10]

See also Intrinsically Disordered Protein.

Relevance

Overexpression of CYCD1 and its catalytic partner CDK4 is seen in human cancer[11]. Overexpression of CYCH and its catalytic partner CDK7 is seen in breast cancer[12].

Structural highlights

All cyclins have an all-α helix fold and share an identical ca. 100 residue domain called 'cyclin box' which binds CDK. Two 5 α-helix cyclin boxes are shown.[13]

3D Structures of Cyclin

Cyclin 3D structures


Cyclin T1 (green) complex with CDK9 (cyan) and TRIS (PDB entry 3blh)

Drag the structure with the mouse to rotate

References

  1. ↑ Silva Cascales H, Burdova K, Middleton A, Kuzin V, Müllers E, Stoy H, Baranello L, Macurek L, Lindqvist A. Cyclin A2 localises in the cytoplasm at the S/G2 transition to activate PLK1. Life Sci Alliance. 2021 Jan 5;4(3):e202000980. PMID:33402344 doi:10.26508/lsa.202000980
  2. ↑ Galderisi U, Jori FP, Giordano A. Cell cycle regulation and neural differentiation. Oncogene. 2003 Aug 11;22(33):5208-19. PMID:12910258 doi:http://dx.doi.org/10.1038/sj.onc.1206558
  3. ↑ Valay JG, Dubois MF, Bensaude O, Faye G. Ccl1, a cyclin associated with protein kinase Kin28, controls the phosphorylation of RNA polymerase II largest subunit and mRNA transcription. C R Acad Sci III. 1996 Mar;319(3):183-9 PMID:8761664
  4. ↑ Sage J. Cyclin C makes an entry into the cell cycle. Dev Cell. 2004 May;6(5):607-8. PMID:15130482
  5. ↑ Jackman M, Kubota Y, den Elzen N, Hagting A, Pines J. Cyclin A- and cyclin E-Cdk complexes shuttle between the nucleus and the cytoplasm. Mol Biol Cell. 2002 Mar;13(3):1030-45. doi: 10.1091/mbc.01-07-0361. PMID:11907280 doi:http://dx.doi.org/10.1091/mbc.01-07-0361
  6. ↑ Galper J, Rayner SL, Hogan AL, Fifita JA, Lee A, Chung RS, Blair IP, Yang S. Cyclin F: A component of an E3 ubiquitin ligase complex with roles in neurodegeneration and cancer. Int J Biochem Cell Biol. 2017 Aug;89:216-220. PMID:28652210 doi:10.1016/j.biocel.2017.06.011
  7. ↑ Peng C, Yang Y, Ji L, Yang P, Yang X, Zhang Y. Cyclin H predicts the poor prognosis and promotes the proliferation of ovarian cancer. Cancer Cell Int. 2020 Jul 16;20:316. PMID:32694938 doi:10.1186/s12935-020-01406-5
  8. ↑ Blazek D, Kohoutek J, Bartholomeeusen K, Johansen E, Hulinkova P, Luo Z, Cimermancic P, Ule J, Peterlin BM. The Cyclin K/Cdk12 complex maintains genomic stability via regulation of expression of DNA damage response genes. Genes Dev. 2011 Oct 15;25(20):2158-72. doi: 10.1101/gad.16962311. PMID:22012619 doi:http://dx.doi.org/10.1101/gad.16962311
  9. ↑ Garriga J, Grana X. Cellular control of gene expression by T-type cyclin/CDK9 complexes. Gene. 2004 Aug 4;337:15-23. doi: 10.1016/j.gene.2004.05.007. PMID:15276198 doi:http://dx.doi.org/10.1016/j.gene.2004.05.007
  10. ↑ Mittnacht S, Boshoff C. Viral cyclins. Rev Med Virol. 2000 May-Jun;10(3):175-84. PMID:10815028
  11. ↑ Jirawatnotai S, Sharma S, Michowski W, Suktitipat B, Geng Y, Quackenbush J, Elias JE, Gygi SP, Wang YE, Sicinski P. The cyclin D1-CDK4 oncogenic interactome enables identification of potential novel oncogenes and clinical prognosis. Cell Cycle. 2014;13(18):2889-900. doi: 10.4161/15384101.2014.946850. PMID:25486477 doi:http://dx.doi.org/10.4161/15384101.2014.946850
  12. ↑ Patel H, Abduljabbar R, Lai CF, Periyasamy M, Harrod A, Gemma C, Steel JH, Patel N, Busonero C, Jerjees D, Remenyi J, Smith S, Gomm JJ, Magnani L, Gyorffy B, Jones LJ, Fuller-Pace F, Shousha S, Buluwela L, Rakha EA, Ellis IO, Coombes RC, Ali S. Expression of CDK7, Cyclin H, and MAT1 Is Elevated in Breast Cancer and Is Prognostic in Estrogen Receptor-Positive Breast Cancer. Clin Cancer Res. 2016 Dec 1;22(23):5929-5938. doi: 10.1158/1078-0432.CCR-15-1104., Epub 2016 Jun 14. PMID:27301701 doi:http://dx.doi.org/10.1158/1078-0432.CCR-15-1104
  13. ↑ Noble ME, Endicott JA, Brown NR, Johnson LN. The cyclin box fold: protein recognition in cell-cycle and transcription control. Trends Biochem Sci. 1997 Dec;22(12):482-7. PMID:9433129

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