Cyclin A2
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| Location (UCSC) | Chr 4: 121.82 – 121.82 Mb | Chr 3: 36.62 – 36.63 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Cyclin-A2 is a
Function
Cyclin A2 belongs to the
Cyclin A2 is synthesized at the onset of S phase and localizes to the nucleus, where the cyclin A2-CDK2 complex is implicated in the initiation and progression of DNA synthesis. Phosphorylation of CDC6 and MCM4 by the cyclin A2-CDK2 complex prevents re-replication of DNA during the cell cycle.[6]
Cyclin A2 is involved in the G2/M transition but it cannot independently form a maturation promoting factor (MPF).[8] Recent studies have shown that the cyclin A2-CDK1 complex triggers cyclin B1-CDK1 activation which results in chromatin condensation and the breakdown of the nuclear envelope.[9]
Regulation
The levels of cyclin A2 are tightly synchronized with the progression of the cell cycle.[10] Transcription initiates in late G1, peaks and plateaus in mid-S, and declines in G2.[10][6]
Cyclin A2 transcription is mostly regulated by the transcription factor
Interactions
Cyclin A2 has been shown to
DNA Repair
Cyclin A2 regulates
During mouse development and aging, cyclin A2 promotes DNA repair, particularly double-strand break repair, in the brain.[22] Also in mice, cyclin A2 was found to be an RNA binding protein that controls the translation of Mre11 mRNA.[23]
Clinical significance
Cyclin A2 (Ccna2) is a key protein involved in the direction of mammalian cardiac myocytes to grow and divide, and has been shown to induce cardiac repair following myocardial infarction.[24] Normally, Ccna2 is silenced postnatally in mammalian cardiac myocytes. Because of this gene silencing, adult heart muscle cells cannot divide readily to repair and regenerate after a heart attack.[24]
Ccna2 has been found to induce cardiac repair in small-animal models following myocardial infarction.[24] Preclinical trials involving injections of adenovirus which contained the Ccna2 gene into infarcted porcine (pig) hearts has shown to be protective of MI in pig hearts.[24] Ccna2 mediated cardiac repair showed both a decrease in fibrosis in the peri-infarct tissue and a greater number of cardiomyocytes at the sites of injection.[24] Delivery of Ccna2 into cardiac tissue invokes a regenerative response and markedly enhances cardiac function.[24][25][26]
Cancer
Increased expression of cyclin A2 has been observed in many types of cancer such as breast, cervical, liver, and lung among others.
Overexpression of cyclin A2 in mammalian cells can result in the delayed onset of metaphase and anaphase.[31] It is also possible that cyclin A2-CDK contributes to tumorigenesis by the phosphorylation of oncoproteins or tumor suppressors like p53.[32]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000145386 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027715 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 1675006.
- ^ S2CID 97398.
- PMID 1312467.
- PMID 17344473.
- PMID 20660152.
- ^ PMID 8202514.
- ^ PMID 12851482.
- ^ PMID 7969176.
- PMID 9889196.
- PMID 9566895.
- S2CID 5787920.
- PMID 10673397.
- PMID 8230483.
- S2CID 21761703.
- PMID 15355997.
- S2CID 8884226.
- ^ PMID 29207607.
- PMID 27425845.
- PMID 27708105.
- ^ S2CID 20386712.
- PMID 17382628.
- PMID 21593865.
- S2CID 10543682.
- S2CID 46236286.
- PMID 11299822.
- PMID 9192980.
- PMID 11285279.
- S2CID 4240439.
Further reading
- Bailly E, Pines J, Hunter T, Bornens M (1992). "Cytoplasmic accumulation of cyclin B1 in human cells: association with a detergent-resistant compartment and with the centrosome". J. Cell Sci. 101 (3): 529–545. PMID 1387877.
- Faha B, Ewen ME, Tsai LH, Livingston DM, Harlow E (1992). "Interaction between human cyclin A and adenovirus E1A-associated p107 protein". Science. 255 (5040): 87–90. PMID 1532458.
- Bandara LR, Adamczewski JP, Hunt T, La Thangue NB (1991). "Cyclin A and the retinoblastoma gene product complex with a common transcription factor". Nature. 352 (6332): 249–251. S2CID 1019851.
- Blanquet V, Wang JA, Chenivesse X, Henglein B, Garreau F, Bréchot C, Turleau C (1990). "Assignment of a human cyclin A gene to 4q26-q27". Genomics. 8 (3): 595–597. PMID 1962755.
- Wang J, Chenivesse X, Henglein B, Bréchot C (1990). "Hepatitis B virus integration in a cyclin A gene in a hepatocellular carcinoma". Nature. 343 (6258): 555–557. S2CID 4269638.
- Jeffrey PD, Russo AA, Polyak K, Gibbs E, Hurwitz J, Massagué J, Pavletich NP (1995). "Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex". Nature. 376 (6538): 313–320. S2CID 4361179.
- Castro A, Jaumot M, Vergés M, Agell N, Bachs O (1994). "Microsomal localization of cyclin A and cdk2 in proliferating rat liver cells". Biochem. Biophys. Res. Commun. 201 (3): 1072–1078. PMID 8024548.
- Dyson N, Dembski M, Fattaey A, Ngwu C, Ewen M, Helin K (1993). "Analysis of p107-associated proteins: p107 associates with a form of E2F that differs from pRB-associated E2F-1". J. Virol. 67 (12): 7641–7647. PMID 8230483.
- Li Y, Graham C, Lacy S, Duncan AM, Whyte P (1993). "The adenovirus E1A-associated 130-kD protein is encoded by a member of the retinoblastoma gene family and physically interacts with cyclins A and E". Genes Dev. 7 (12A): 2366–2377. PMID 8253383.
- Lees EM, Harlow E (1993). "Sequences within the conserved cyclin box of human cyclin A are sufficient for binding to and activation of cdc2 kinase". Mol. Cell. Biol. 13 (2): 1194–1201. PMID 8423786.
- Sebastian B, Kakizuka A, Hunter T (1993). "Cdc25M2 activation of cyclin-dependent kinases by dephosphorylation of threonine-14 and tyrosine-15". Proc. Natl. Acad. Sci. U.S.A. 90 (8): 3521–3524. PMID 8475101.
- Carbonaro-Hall D, Williams R, Wu L, Warburton D, Zeichner-David M, MacDougall M, Tolo V, Hall F (1993). "G1 expression and multistage dynamics of cyclin A in human osteosarcoma cells". Oncogene. 8 (6): 1649–1659. PMID 8502485.
- Meikrantz W, Schlegel R (1996). "Suppression of apoptosis by dominant negative mutants of cyclin-dependent protein kinases". J. Biol. Chem. 271 (17): 10205–10209. PMID 8626584.
- Poon RY, Jiang W, Toyoshima H, Hunter T (1996). "Cyclin-dependent kinases are inactivated by a combination of p21 and Thr-14/Tyr-15 phosphorylation after UV-induced DNA damage". J. Biol. Chem. 271 (22): 13283–13291. PMID 8662825.
- Russo AA, Jeffrey PD, Patten AK, Massagué J, Pavletich NP (1996). "Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex". Nature. 382 (6589): 325–331. S2CID 4284942.
- Russo AA, Jeffrey PD, Pavletich NP (1996). "Structural basis of cyclin-dependent kinase activation by phosphorylation". Nat. Struct. Biol. 3 (8): 696–700. S2CID 383015.
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