Cyclin B1

Cyclin B1

PDB rendering based on 2b9r.
Identifiers
Symbols CCNB1; CCNB
External IDs OMIM: 123836 HomoloGene: 68982 GeneCards: CCNB1 Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 891 n/a
Ensembl ENSG00000134057 n/a
UniProt P14635 n/a
RefSeq (mRNA) NM_031966.2 n/a
RefSeq (protein) NP_114172.1 n/a
Location (UCSC) Chr 5:
68.46 – 68.47 Mb		 n/a
PubMed search [1] n/a

G2/mitotic-specific cyclin-B1 is a protein that in humans is encoded by the CCNB1 gene.[1]

Contents

Function

Cyclin B1 is a regulatory protein involved in mitosis. The gene product complexes with p34(cdc2) to form the maturation-promoting factor (MPF). Two alternative transcripts have been found, a constitutively expressed transcript and a cell cycle-regulated transcript, that is expressed predominantly during G2/M phase of the cell cycle. The different transcripts result from the use of alternate transcription initiation sites.[2]

Cyclin B1 contributes to the switch-like all or none behavior of the cell in deciding to commit to mitosis. Its activation is well regulated, and positive feedback loops ensure that once the cyclin B1-Cdk1 complex is activated it is not deactivated. Cyclin B1-Cdk1 is involved in the early events of mitosis such as chromosome condensation, nuclear envelope breakdown, and spindle pole assembly.

Once activated, cyclin B1-Cdk1 promotes several of the events of early mitosis. The active complex phosphorylates and activates 13S Condensin,[3] which helps to condense chromosomes.

Another important function of the cyclin B1-Cdk1 complex is to break down the nuclear envelope. The nuclear envelope is a membranous structure containing large protein complexes supported by a network of nuclear lamins. Phosphorylation of the lamins by cyclin B1-Cdk1 causes them to dissociate,[4] compromising the structural integrity of the nuclear envelope so that it breaks down. The destruction of the nuclear envelope is important because it allows the mitotic spindle to access the chromosomes.

Regulation

Like all cyclins, levels of cyclin B1 oscillate over the course of the cell cycle. Just prior to mitosis, a large amount of cyclin B1 is present in the cell, but it is inactive due to phosphorylation of Cdk1 by the Wee1 kinase. The complex is activated by dephosphorylation by the phosphatase Cdc25.[5] Cdc25 is always present in the cell but must be activated by phosphorylation. A possible trigger for activation is phosphorylation by cyclin A-Cdk, which functions before cyclin B1-Cdk in the cell cycle. Active Cdk1 is also capable of phosphorylating and activating Cdc25 and thus promote its own activation, resulting in a positive feedback loop. Once cyclin B1-Cdk1 is activated, it remains stably active for the rest of mitosis.

Another mechanism by which cyclin B1-Cdk1 activity is regulated is through subcellular localization. Before mitosis almost all cyclin B1 in the cell is located in the cytoplasm, but in late prophase it relocates to the nucleus. This is regulated by the phosphorylation of cyclin B1, in contrast to phosphorylation of Cdk1 regulating the activity of the complex. Phosphorylation of cyclin B1 causes it to be imported to the nucleus,[6] and phosphorylation also prevents export from the nucleus by blocking the nuclear export signal.[7] Cyclin B1 is phosphorylated by Polo kinase and Cdk1 , again setting up a positive feedback loop that commits cyclin B1-Cdk1 to its fate.

At the end of mitosis, cyclin B1 is targeted for degradation by the APC through its APC localization sequence, permitting the cell to exit mitosis.

Interactions

Cyclin B1 has been shown to interact with Cdk1,[8][9][10][11] GADD45A[12][13] and RALBP1.[14]

See also

References

  1. ^ Sartor H, Ehlert F, Grzeschik KH, Muller R, Adolph S (Aug 1992). "Assignment of two human cell cycle genes, CDC25C and CCNB1, to 5q31 and 5q12, respectively". Genomics 13 (3): 911–2. doi:10.1016/0888-7543(92)90190-4. PMID 1386342. 
  2. ^ "Entrez Gene: CCNB1 cyclin B1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=891. 
  3. ^ Kimura K, Hirano M, Kobayashi R, Hirano T (October 1998). "Phosphorylation and activation of 13S condensin by Cdc2 in vitro". Science 282 (5388): 487–90. doi:10.1126/science.282.5388.487. PMID 9774278. 
  4. ^ Heald R, McKeon F (May 1990). "Mutations of phosphorylation sites in lamin A that prevent nuclear lamina disassembly in mitosis". Cell 61 (4): 579–89. doi:10.1016/0092-8674(90)90470-Y. PMID 2344612. 
  5. ^ Berry LD, Gould KL (1996). "Regulation of Cdc2 activity by phosphorylation at T14/Y15". Prog Cell Cycle Res 2: 99–105. PMID 9552387. 
  6. ^ Hagting A, Jackman M, Simpson K, Pines J (July 1999). "Translocation of cyclin B1 to the nucleus at prophase requires a phosphorylation-dependent nuclear import signal". Curr. Biol. 9 (13): 680–9. doi:10.1016/S0960-9822(99)80308-X. PMID 10395539. 
  7. ^ Yang J, Song H, Walsh S, Bardes ES, Kornbluth S (February 2001). "Combinatorial control of cyclin B1 nuclear trafficking through phosphorylation at multiple sites". J. Biol. Chem. 276 (5): 3604–9. doi:10.1074/jbc.M008151200. PMID 11060306. 
  8. ^ 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. 19 (2): 1460–9. PMC 116074. PMID 9891079. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=116074. 
  9. ^ Yang, Q; Manicone A, Coursen J D, Linke S P, Nagashima M, Forgues M, Wang X W (Nov. 2000). "Identification of a functional domain in a GADD45-mediated G2/M checkpoint". J. Biol. Chem. 275 (47): 36892–8. doi:10.1074/jbc.M005319200. PMID 10973963. 
  10. ^ Pines, J; Hunter T (Sep. 1989). "Isolation of a human cyclin cDNA: evidence for cyclin mRNA and protein regulation in the cell cycle and for interaction with p34cdc2". Cell 58 (5): 833–46. doi:10.1016/0092-8674(89)90936-7. PMID 2570636. 
  11. ^ Kong, M; Barnes E A, Ollendorff V, Donoghue D J (Mar. 2000). "Cyclin F regulates the nuclear localization of cyclin B1 through a cyclin-cyclin interaction". EMBO J. 19 (6): 1378–88. doi:10.1093/emboj/19.6.1378. PMC 305678. PMID 10716937. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=305678. 
  12. ^ Zhan, Q; Antinore M J, Wang X W, Carrier F, Smith M L, Harris C C, Fornace A J (May. 1999). "Association with Cdc2 and inhibition of Cdc2/Cyclin B1 kinase activity by the p53-regulated protein Gadd45". Oncogene 18 (18): 2892–900. doi:10.1038/sj.onc.1202667. PMID 10362260. 
  13. ^ Vairapandi, Mariappan; Balliet Arthur G, Hoffman Barbara, Liebermann Dan A (Sep. 2002). "GADD45b and GADD45g are cdc2/cyclinB1 kinase inhibitors with a role in S and G2/M cell cycle checkpoints induced by genotoxic stress". J. Cell. Physiol. 192 (3): 327–38. doi:10.1002/jcp.10140. PMID 12124778. 
  14. ^ Rossé, Carine; L'Hoste Sébastien, Offner Nicolas, Picard André, Camonis Jacques (Aug. 2003). "RLIP, an effector of the Ral GTPases, is a platform for Cdk1 to phosphorylate epsin during the switch off of endocytosis in mitosis". J. Biol. Chem. 278 (33): 30597–604. doi:10.1074/jbc.M302191200. PMID 12775724. 

Further reading

Cyclin
A (A1, A2) · B (B1, B2, B3) · D (D1, D2, D3) · E (E1, E2)
CDK
2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · CDK-activating kinase
CDK inhibitor
P53 p63 p73 family
p53 · p63 · p73
Phases and
checkpoints
Other cellular phases
B bsyn: dna (repl, cycl, reco, repr) · tscr (fact, tcrg, nucl, rnat, rept, ptts) · tltn (risu, pttl, nexn) · dnab, rnab/runp · stru (domn, 1°, 2°, 3°, 4°)