Europe PMC
Nothing Special   »   [go: up one dir, main page]

Europe PMC requires Javascript to function effectively.

Either your web browser doesn't support Javascript or it is currently turned off. In the latter case, please turn on Javascript support in your web browser and reload this page.

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy.

The differential localization of human cyclins A and B is due to a cytoplasmic retention signal in cyclin B.

Author information

Affiliations

  • 1. Wellcome/CRC Institute, Cambridge, UK.
      Authors
    • Pines J 1
    (1 author)

The EMBO Journal, 01 Aug 1994, 13(16):3772-3781
https://doi.org/10.1002/j.1460-2075.1994.tb06688.x PMID: 8070405 PMCID: PMC395290

Free full text in Europe PMC

Abstract 

We have shown previously that human cyclins A and B1 are localized differentially in the cell during interphase; cyclin A is nuclear and cyclin B1 is a cytoplasmic protein. To understand the basis of this difference we created deletion mutants and various chimeras between the two types of cyclin and expressed them in tissue culture cells by transient transfection. We find that the N-terminus of cyclin B1 contains a 42 amino acid region that is sufficient to retain the normally nuclear cyclin A in the cytoplasm. Conversely, deleting the cytoplasmic retention signal region from cyclin B1 causes the protein to become nuclear. Although the cytoplasmic retention signal region is outside the cyclin box, its sequence is well conserved in human cyclin B2, and is both necessary and sufficient to keep cyclin B2 in the cytoplasm. Thus we propose that the subcellular distribution of the B-type cyclins is determined primarily by a small region of the N-terminus which targets the cyclin--CDK complexes to particular structures in the cytoplasm.

Free full text 

Logo of embojLink to Publisher's site
EMBO J. 1994 Aug 15; 13(16): 3772–3781.
PMCID: PMC395290
PMID: 8070405

The differential localization of human cyclins A and B is due to a cytoplasmic retention signal in cyclin B.

J Pines and T Hunter
Author information Copyright and License information Disclaimer

Abstract

We have shown previously that human cyclins A and B1 are localized differentially in the cell during interphase; cyclin A is nuclear and cyclin B1 is a cytoplasmic protein. To understand the basis of this difference we created deletion mutants and various chimeras between the two types of cyclin and expressed them in tissue culture cells by transient transfection. We find that the N-terminus of cyclin B1 contains a 42 amino acid region that is sufficient to retain the normally nuclear cyclin A in the cytoplasm. Conversely, deleting the cytoplasmic retention signal region from cyclin B1 causes the protein to become nuclear. Although the cytoplasmic retention signal region is outside the cyclin box, its sequence is well conserved in human cyclin B2, and is both necessary and sufficient to keep cyclin B2 in the cytoplasm. Thus we propose that the subcellular distribution of the B-type cyclins is determined primarily by a small region of the N-terminus which targets the cyclin--CDK complexes to particular structures in the cytoplasm.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (3.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
 
icon of scanned page 3772
3772
icon of scanned page 3773
3773
icon of scanned page 3774
3774
icon of scanned page 3775
3775
icon of scanned page 3776
3776
icon of scanned page 3777
3777
icon of scanned page 3778
3778
icon of scanned page 3779
3779
icon of scanned page 3780
3780
icon of scanned page 3781
3781
 

Images in this article

Image
Image
on p.3774
Image
Image
on p.3775
Image
Image
on p.3776
Image
Image
on p.3776
Image
Image
on p.3777
Image
Image
on p.3778
Image
Image
on p.3778
Image
Image
on p.3779
Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Alfa CE, Ducommun B, Beach D, Hyams JS. Distinct nuclear and spindle pole body population of cyclin-cdc2 in fission yeast. Nature. 1990 Oct 18;347(6294):680–682. [Abstract] [Google Scholar]
  • Bailly E, Dorée M, Nurse P, Bornens M. p34cdc2 is located in both nucleus and cytoplasm; part is centrosomally associated at G2/M and enters vesicles at anaphase. EMBO J. 1989 Dec 20;8(13):3985–3995. [Europe PMC free article] [Abstract] [Google Scholar]
  • Bailly E, Pines J, Hunter T, Bornens M. Cytoplasmic accumulation of cyclin B1 in human cells: association with a detergent-resistant compartment and with the centrosome. J Cell Sci. 1992 Mar;101(Pt 3):529–545. [Abstract] [Google Scholar]
  • Baldin V, Lukas J, Marcote MJ, Pagano M, Draetta G. Cyclin D1 is a nuclear protein required for cell cycle progression in G1. Genes Dev. 1993 May;7(5):812–821. [Abstract] [Google Scholar]
  • Brizuela L, Draetta G, Beach D. p13suc1 acts in the fission yeast cell division cycle as a component of the p34cdc2 protein kinase. EMBO J. 1987 Nov;6(11):3507–3514. [Europe PMC free article] [Abstract] [Google Scholar]
  • De Bondt HL, Rosenblatt J, Jancarik J, Jones HD, Morgan DO, Kim SH. Crystal structure of cyclin-dependent kinase 2. Nature. 1993 Jun 17;363(6430):595–602. [Abstract] [Google Scholar]
  • Draetta G. Cdc2 activation: the interplay of cyclin binding and Thr161 phosphorylation. Trends Cell Biol. 1993 Sep;3(9):287–289. [Abstract] [Google Scholar]
  • el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B. WAF1, a potential mediator of p53 tumor suppression. Cell. 1993 Nov 19;75(4):817–825. [Abstract] [Google Scholar]
  • Fesquet D, Labbé JC, Derancourt J, Capony JP, Galas S, Girard F, Lorca T, Shuttleworth J, Dorée M, Cavadore JC. The MO15 gene encodes the catalytic subunit of a protein kinase that activates cdc2 and other cyclin-dependent kinases (CDKs) through phosphorylation of Thr161 and its homologues. EMBO J. 1993 Aug;12(8):3111–3121. [Europe PMC free article] [Abstract] [Google Scholar]
  • Galaktionov K, Beach D. Specific activation of cdc25 tyrosine phosphatases by B-type cyclins: evidence for multiple roles of mitotic cyclins. Cell. 1991 Dec 20;67(6):1181–1194. [Abstract] [Google Scholar]
  • Gallant P, Nigg EA. Cyclin B2 undergoes cell cycle-dependent nuclear translocation and, when expressed as a non-destructible mutant, causes mitotic arrest in HeLa cells. J Cell Biol. 1992 Apr;117(1):213–224. [Europe PMC free article] [Abstract] [Google Scholar]
  • Girard F, Strausfeld U, Fernandez A, Lamb NJ. Cyclin A is required for the onset of DNA replication in mammalian fibroblasts. Cell. 1991 Dec 20;67(6):1169–1179. [Abstract] [Google Scholar]
  • Girard F, Strausfeld U, Cavadore JC, Russell P, Fernandez A, Lamb NJ. cdc25 is a nuclear protein expressed constitutively throughout the cell cycle in nontransformed mammalian cells. J Cell Biol. 1992 Aug;118(4):785–794. [Europe PMC free article] [Abstract] [Google Scholar]
  • Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 1993 Nov 19;75(4):805–816. [Abstract] [Google Scholar]
  • Heald R, McLoughlin M, McKeon F. Human wee1 maintains mitotic timing by protecting the nucleus from cytoplasmically activated Cdc2 kinase. Cell. 1993 Aug 13;74(3):463–474. [Abstract] [Google Scholar]
  • Horton RM, Cai ZL, Ho SN, Pease LR. Gene splicing by overlap extension: tailor-made genes using the polymerase chain reaction. Biotechniques. 1990 May;8(5):528–535. [Abstract] [Google Scholar]
  • Hunt T. Cyclins and their partners: from a simple idea to complicated reality. Semin Cell Biol. 1991 Aug;2(4):213–222. [Abstract] [Google Scholar]
  • Knighton DR, Zheng JH, Ten Eyck LF, Ashford VA, Xuong NH, Taylor SS, Sowadski JM. Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase. Science. 1991 Jul 26;253(5018):407–414. [Abstract] [Google Scholar]
  • Kobayashi H, Stewart E, Poon R, Adamczewski JP, Gannon J, Hunt T. Identification of the domains in cyclin A required for binding to, and activation of, p34cdc2 and p32cdk2 protein kinase subunits. Mol Biol Cell. 1992 Nov;3(11):1279–1294. [Europe PMC free article] [Abstract] [Google Scholar]
  • Lees EM, Harlow E. Sequences within the conserved cyclin box of human cyclin A are sufficient for binding to and activation of cdc2 kinase. Mol Cell Biol. 1993 Feb;13(2):1194–1201. [Europe PMC free article] [Abstract] [Google Scholar]
  • Maridor G, Gallant P, Golsteyn R, Nigg EA. Nuclear localization of vertebrate cyclin A correlates with its ability to form complexes with cdk catalytic subunits. J Cell Sci. 1993 Oct;106(Pt 2):535–544. [Abstract] [Google Scholar]
  • Meijer L, Arion D, Golsteyn R, Pines J, Brizuela L, Hunt T, Beach D. Cyclin is a component of the sea urchin egg M-phase specific histone H1 kinase. EMBO J. 1989 Aug;8(8):2275–2282. [Europe PMC free article] [Abstract] [Google Scholar]
  • Millar JB, Blevitt J, Gerace L, Sadhu K, Featherstone C, Russell P. p55CDC25 is a nuclear protein required for the initiation of mitosis in human cells. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10500–10504. [Europe PMC free article] [Abstract] [Google Scholar]
  • Nigg EA. Cellular substrates of p34(cdc2) and its companion cyclin-dependent kinases. Trends Cell Biol. 1993 Sep;3(9):296–301. [Abstract] [Google Scholar]
  • Nurse P. Universal control mechanism regulating onset of M-phase. Nature. 1990 Apr 5;344(6266):503–508. [Abstract] [Google Scholar]
  • Ookata K, Hisanaga S, Okano T, Tachibana K, Kishimoto T. Relocation and distinct subcellular localization of p34cdc2-cyclin B complex at meiosis reinitiation in starfish oocytes. EMBO J. 1992 May;11(5):1763–1772. [Europe PMC free article] [Abstract] [Google Scholar]
  • Ookata K, Hisanaga S, Okumura E, Kishimoto T. Association of p34cdc2/cyclin B complex with microtubules in starfish oocytes. J Cell Sci. 1993 Aug;105(Pt 4):873–881. [Abstract] [Google Scholar]
  • Pagano M, Pepperkok R, Verde F, Ansorge W, Draetta G. Cyclin A is required at two points in the human cell cycle. EMBO J. 1992 Mar;11(3):961–971. [Europe PMC free article] [Abstract] [Google Scholar]
  • Peter M, Nakagawa J, Dorée M, Labbé JC, Nigg EA. In vitro disassembly of the nuclear lamina and M phase-specific phosphorylation of lamins by cdc2 kinase. Cell. 1990 May 18;61(4):591–602. [Abstract] [Google Scholar]
  • Pines J. Cyclins: wheels within wheels. Cell Growth Differ. 1991 Jun;2(6):305–310. [Abstract] [Google Scholar]
  • Pines J. Clear as crystal? Curr Biol. 1993 Aug 1;3(8):544–547. [Abstract] [Google Scholar]
  • Pines J, Hunter T. Isolation of a human cyclin cDNA: evidence for cyclin mRNA and protein regulation in the cell cycle and for interaction with p34cdc2. Cell. 1989 Sep 8;58(5):833–846. [Abstract] [Google Scholar]
  • Pines J, Hunter T. Cyclin-dependent kinases: a new cell cycle motif? Trends Cell Biol. 1991 Nov;1(5):117–121. [Abstract] [Google Scholar]
  • Pines J, Hunter T. Human cyclins A and B1 are differentially located in the cell and undergo cell cycle-dependent nuclear transport. J Cell Biol. 1991 Oct;115(1):1–17. [Europe PMC free article] [Abstract] [Google Scholar]
  • Poon RY, Yamashita K, Adamczewski JP, Hunt T, Shuttleworth J. The cdc2-related protein p40MO15 is the catalytic subunit of a protein kinase that can activate p33cdk2 and p34cdc2. EMBO J. 1993 Aug;12(8):3123–3132. [Europe PMC free article] [Abstract] [Google Scholar]
  • Reed SI, Wittenberg C, Lew DJ, Dulic V, Henze M. G1 control in yeast and animal cells. Cold Spring Harb Symp Quant Biol. 1991;56:61–67. [Abstract] [Google Scholar]
  • Robbins J, Dilworth SM, Laskey RA, Dingwall C. Two interdependent basic domains in nucleoplasmin nuclear targeting sequence: identification of a class of bipartite nuclear targeting sequence. Cell. 1991 Feb 8;64(3):615–623. [Abstract] [Google Scholar]
  • Schmidt-Zachmann MS, Dargemont C, Kühn LC, Nigg EA. Nuclear export of proteins: the role of nuclear retention. Cell. 1993 Aug 13;74(3):493–504. [Abstract] [Google Scholar]
  • Sherr CJ. Mammalian G1 cyclins. Cell. 1993 Jun 18;73(6):1059–1065. [Abstract] [Google Scholar]
  • Solomon MJ, Harper JW, Shuttleworth J. CAK, the p34cdc2 activating kinase, contains a protein identical or closely related to p40MO15. EMBO J. 1993 Aug;12(8):3133–3142. [Europe PMC free article] [Abstract] [Google Scholar]
  • Verde F, Dogterom M, Stelzer E, Karsenti E, Leibler S. Control of microtubule dynamics and length by cyclin A- and cyclin B-dependent kinases in Xenopus egg extracts. J Cell Biol. 1992 Sep;118(5):1097–1108. [Europe PMC free article] [Abstract] [Google Scholar]
  • Waga S, Hannon GJ, Beach D, Stillman B. The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature. 1994 Jun 16;369(6481):574–578. [Abstract] [Google Scholar]
  • Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D. p21 is a universal inhibitor of cyclin kinases. Nature. 1993 Dec 16;366(6456):701–704. [Abstract] [Google Scholar]
  • Yamashiro S, Yamakita Y, Hosoya H, Matsumura F. Phosphorylation of non-muscle caldesmon by p34cdc2 kinase during mitosis. Nature. 1991 Jan 10;349(6305):169–172. [Abstract] [Google Scholar]
  • Zheng XF, Ruderman JV. Functional analysis of the P box, a domain in cyclin B required for the activation of Cdc25. Cell. 1993 Oct 8;75(1):155–164. [Abstract] [Google Scholar]
  • Zindy F, Lamas E, Chenivesse X, Sobczak J, Wang J, Fesquet D, Henglein B, Bréchot C. Cyclin A is required in S phase in normal epithelial cells. Biochem Biophys Res Commun. 1992 Feb 14;182(3):1144–1154. [Abstract] [Google Scholar]
Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

Full text links 

Read article at publisher's site: https://doi.org/10.1002/j.1460-2075.1994.tb06688.x

Read article for free, from open access legal sources, via Unpaywall: https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/j.1460-2075.1994.tb06688.xUnpaywall

Citations & impact 

Impact metrics

146
Citations
Jump to Citations

Citations of article over time

Alternative metrics

Altmetric item for https://www.altmetric.com/details/5310185
Altmetric
Discover the attention surrounding your research
https://www.altmetric.com/details/5310185

Article citations

Go to all (146) article citations

Other citations

Similar Articles 

To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.

Funding 

Funders who supported this work.

NCI NIH HHS (1)

Wellcome Trust