Cyclin E1

Cyclin E1
PDB rendering based on 1w98.
Available structures PDB 1w98
Identifiers
Symbols	CCNE1; CCNE
External IDs	OMIM: 123837 MGI: 88316 HomoloGene: 14452 GeneCards: CCNE1 Gene
Gene Ontology Molecular function • transcription coactivator activity • protein binding • kinase activity • cyclin-dependent protein kinase regulator activity • protein kinase binding • protein complex binding • androgen receptor binding Cellular component • cyclin-dependent protein kinase holoenzyme complex • nucleus • nucleus • nucleoplasm • nucleoplasm • nucleolus • cytoplasm • centrosome • cytosol Biological process • regulation of cyclin-dependent protein kinase activity • G1/S transition of mitotic cell cycle • G1/S transition of mitotic cell cycle • regulation of transcription involved in G1/S phase of mitotic cell cycle • mitotic cell cycle • antral ovarian follicle growth • liver development • DNA-dependent DNA replication initiation • protein phosphorylation • response to organic nitrogen • response to purine-containing compound • Wnt receptor signaling pathway • androgen receptor signaling pathway • organ regeneration • cellular response to nutrient • response to estradiol stimulus • response to progesterone stimulus • response to vitamin E • response to cytokine stimulus • response to drug • response to ethanol • positive regulation of cell differentiation • positive regulation of transcription, DNA-dependent • cell division • response to corticosterone stimulus • response to methylmercury Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	898	12447
Ensembl	ENSG00000105173	ENSMUSG00000002068
UniProt	P24864	A0JLN2
RefSeq (mRNA)	NM_001238.1	NM_007633.2
RefSeq (protein)	NP_001229.1	NP_031659.2
Location (UCSC)	Chr 19: 30.3 – 30.32 Mb	Chr 7: 38.88 – 38.89 Mb
PubMed search	[1]	[2]

G1/S-specific cyclin-E1 is a protein that in humans is encoded by the CCNE1 gene.^[1]

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 which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK2, whose activity is required for cell cycle G1/S transition. This protein accumulates at the G1-S phase boundary and is degraded as cells progress through S phase. Overexpression of this gene has been observed in many tumors, which results in chromosome instability, and thus may contribute to tumorigenesis. This protein was found to associate with, and be involved in, the phosphorylation of NPAT protein (nuclear protein mapped to the ATM locus), which participates in cell-cycle regulated histone gene expression and plays a critical role in promoting cell-cycle progression in the absence of pRB. Two alternatively spliced transcript variants of this gene, which encode distinct isoforms, have been described. Two additional splice variants were reported but detailed nucleotide sequence information is not yet available.^[2]

See also

• cyclin E

Interactions

Cyclin E1 has been shown to interact with Retinoblastoma-like protein 2,^[3][4] Cdk1,^[3][5] CDC25A,^[3][6] Cyclin-dependent kinase 2,^{[3][5][7][8][9][10]} SMARCA4,^[3][11] CDKN1B,^[3][9] HERC5,^[12] CUL3^[13] and P21.^[7]

References

1. ^ Lew DJ, Dulic V, Reed SI (Oct 1991). "Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast". Cell 66 (6): 1197–206. doi:10.1016/0092-8674(91)90042-W. PMID 1833066. 
2. ^ "Entrez Gene: CCNE1 cyclin E1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=898. 
3. ^ ^{a b c d e f} Shanahan, F; Seghezzi W, Parry D, Mahony D, Lees E (Feb. 1999). "Cyclin E associates with BAF155 and BRG1, components of the mammalian SWI-SNF complex, and alters the ability of BRG1 to induce growth arrest". Mol. Cell. Biol. (UNITED STATES) 19 (2): 1460–9. ISSN 0270-7306. PMC 116074. PMID 9891079. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=116074. 
4. ^ Li, Y; Graham C, Lacy S, Duncan A M, Whyte P (Dec. 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. (UNITED STATES) 7 (12A): 2366–77. doi:10.1101/gad.7.12a.2366. ISSN 0890-9369. PMID 8253383. 
5. ^ ^{a b} Koff, A; Giordano A, Desai D, Yamashita K, Harper J W, Elledge S, Nishimoto T, Morgan D O, Franza B R, Roberts J M (Sep. 1992). "Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle". Science (UNITED STATES) 257 (5077): 1689–94. doi:10.1126/science.1388288. ISSN 0036-8075. PMID 1388288. 
6. ^ Xu, X; Burke S P (Mar. 1996). "Roles of active site residues and the NH2-terminal domain in the catalysis and substrate binding of human Cdc25". J. Biol. Chem. (UNITED STATES) 271 (9): 5118–24. doi:10.1074/jbc.271.9.5118. ISSN 0021-9258. PMID 8617791. 
7. ^ ^{a b} McKenzie, Pamela P; Danks Mary K, Kriwacki Richard W, Harris Linda C (Jul. 2003). "P21Waf1/Cip1 dysfunction in neuroblastoma: a novel mechanism of attenuating G0-G1 cell cycle arrest". Cancer Res. (United States) 63 (13): 3840–4. ISSN 0008-5472. PMID 12839982. 
8. ^ Mayer, Christine; Zhao Jian, Yuan Xuejun, Grummt Ingrid (Feb. 2004). "mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability". Genes Dev. (United States) 18 (4): 423–34. doi:10.1101/gad.285504. ISSN 0890-9369. PMC 359396. PMID 15004009. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=359396. 
9. ^ ^{a b} Connor, Michael K; Kotchetkov Rouslan, Cariou Sandrine, Resch Ansgar, Lupetti Rafaella, Beniston Richard G, Melchior Frauke, Hengst Ludger, Slingerland Joyce M (Jan. 2003). "CRM1/Ran-mediated nuclear export of p27(Kip1) involves a nuclear export signal and links p27 export and proteolysis". Mol. Biol. Cell (United States) 14 (1): 201–13. doi:10.1091/mbc.E02-06-0319. ISSN 1059-1524. PMC 140238. PMID 12529437. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=140238. 
10. ^ Boudrez, A; Beullens M, Groenen P, Van Eynde A, Vulsteke V, Jagiello I, Murray M, Krainer A R, Stalmans W, Bollen M (Aug. 2000). "NIPP1-mediated interaction of protein phosphatase-1 with CDC5L, a regulator of pre-mRNA splicing and mitotic entry". J. Biol. Chem. (UNITED STATES) 275 (33): 25411–7. doi:10.1074/jbc.M001676200. ISSN 0021-9258. PMID 10827081. 
11. ^ Wong, A K; Shanahan F, Chen Y, Lian L, Ha P, Hendricks K, Ghaffari S, Iliev D, Penn B, Woodland A M, Smith R, Salada G, Carillo A, Laity K, Gupte J, Swedlund B, Tavtigian S V, Teng D H, Lees E (Nov. 2000). "BRG1, a component of the SWI-SNF complex, is mutated in multiple human tumor cell lines". Cancer Res. (UNITED STATES) 60 (21): 6171–7. ISSN 0008-5472. PMID 11085541. 
12. ^ Mitsui, K; Nakanishi M, Ohtsuka S, Norwood T H, Okabayashi K, Miyamoto C, Tanaka K, Yoshimura A, Ohtsubo M (Dec. 1999). "A novel human gene encoding HECT domain and RCC1-like repeats interacts with cyclins and is potentially regulated by the tumor suppressor proteins". Biochem. Biophys. Res. Commun. (UNITED STATES) 266 (1): 115–22. doi:10.1006/bbrc.1999.1777. ISSN 0006-291X. PMID 10581175. 
13. ^ Singer, J D; Gurian-West M, Clurman B, Roberts J M (Sep. 1999). "Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells". Genes Dev. (UNITED STATES) 13 (18): 2375–87. doi:10.1101/gad.13.18.2375. ISSN 0890-9369. PMC 317026. PMID 10500095. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=317026. 

Further reading

• Akita H (2003). "[Prognostic importance of altered expression of cell cycle regulators in lung cancer]". Nippon Rinsho. 60 Suppl 5: 267–71. PMID 12101670. 
• Mazumder S, DuPree EL, Almasan A (2004). "A dual role of cyclin E in cell proliferation and apoptosis may provide a target for cancer therapy.". Current cancer drug targets 4 (1): 65–75. doi:10.2174/1568009043481669. PMC 1307511. PMID 14965268. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1307511. 
• Hinds PW, Mittnacht S, Dulic V, et al. (1992). "Regulation of retinoblastoma protein functions by ectopic expression of human cyclins.". Cell 70 (6): 993–1006. doi:10.1016/0092-8674(92)90249-C. PMID 1388095. 
• Koff A, Giordano A, Desai D, et al. (1992). "Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle.". Science 257 (5077): 1689–94. doi:10.1126/science.1388288. PMID 1388288. 
• Koff A, Cross F, Fisher A, et al. (1991). "Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene family.". Cell 66 (6): 1217–28. doi:10.1016/0092-8674(91)90044-Y. PMID 1833068. 
• Demetrick DJ, Matsumoto S, Hannon GJ, et al. (1995). "Chromosomal mapping of the genes for the human cell cycle proteins cyclin C (CCNC), cyclin E (CCNE), p21 (CDKN1) and KAP (CDKN3).". Cytogenet. Cell Genet. 69 (3-4): 190–2. doi:10.1159/000133960. PMID 7698009. 
• Ohtsubo M, Theodoras AM, Schumacher J, et al. (1995). "Human cyclin E, a nuclear protein essential for the G1-to-S phase transition.". Mol. Cell. Biol. 15 (5): 2612–24. PMC 230491. PMID 7739542. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=230491. 
• Sewing A, Rönicke V, Bürger C, et al. (1994). "Alternative splicing of human cyclin E.". J. Cell. Sci.. 107 ( Pt 2): 581–8. PMID 8207080. 
• Dyson N, Dembski M, Fattaey A, et al. (1993). "Analysis of p107-associated proteins: p107 associates with a form of E2F that differs from pRB-associated E2F-1.". J. Virol. 67 (12): 7641–7. PMC 238233. PMID 8230483. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=238233. 
• Li Y, Graham C, Lacy S, et al. (1994). "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): 2366–77. doi:10.1101/gad.7.12a.2366. PMID 8253383. 
• Xu X, Burke SP (1996). "Roles of active site residues and the NH2-terminal domain in the catalysis and substrate binding of human Cdc25.". J. Biol. Chem. 271 (9): 5118–24. doi:10.1074/jbc.271.9.5118. PMID 8617791. 
• Ohtani K, DeGregori J, Nevins JR (1996). "Regulation of the cyclin E gene by transcription factor E2F1.". Proc. Natl. Acad. Sci. U.S.A. 92 (26): 12146–50. doi:10.1073/pnas.92.26.12146. PMC 40313. PMID 8618861. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=40313. 
• Geng Y, Eaton EN, Picón M, et al. (1996). "Regulation of cyclin E transcription by E2Fs and retinoblastoma protein.". Oncogene 12 (6): 1173–80. PMID 8649818. 
• 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): 13283–91. doi:10.1074/jbc.271.22.13283. PMID 8662825. 
• Chen J, Saha P, Kornbluth S, et al. (1996). "Cyclin-binding motifs are essential for the function of p21CIP1.". Mol. Cell. Biol. 16 (9): 4673–82. PMC 231467. PMID 8756624. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=231467. 
• Li H, Lahti JM, Valentine M, et al. (1997). "Molecular cloning and chromosomal localization of the human cyclin C (CCNC) and cyclin E (CCNE) genes: deletion of the CCNC gene in human tumors.". Genomics 32 (2): 253–9. doi:10.1006/geno.1996.0112. PMID 8833152. 
• Won KA, Reed SI (1996). "Activation of cyclin E/CDK2 is coupled to site-specific autophosphorylation and ubiquitin-dependent degradation of cyclin E.". EMBO J. 15 (16): 4182–93. PMC 452142. PMID 8861947. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=452142. 
• Sala A, Kundu M, Casella I, et al. (1997). "Activation of human B-MYB by cyclins.". Proc. Natl. Acad. Sci. U.S.A. 94 (2): 532–6. doi:10.1073/pnas.94.2.532. PMC 19547. PMID 9012818. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=19547. 
• Mumberg D, Wick M, Bürger C, et al. (1997). "Cyclin ET, a new splice variant of human cyclin E with a unique expression pattern during cell cycle progression and differentiation.". Nucleic Acids Res. 25 (11): 2098–105. doi:10.1093/nar/25.11.2098. PMC 146711. PMID 9153308. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=146711.