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PMID: 19592082 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Cyclin A is redundant in fibroblasts but essential in hematopoietic and embryonic stem cells.

Cell ·Vol. 138 ·No. 2 ·2009-07-23 ·Pages 352-65

Kalaszczynska I, Geng Y, Iino T, Mizuno S, Choi Y, Kondratiuk I, Silver DP, Wolgemuth DJ, Akashi K, Sicinski P

Abstract

Cyclins are regulatory subunits of cyclin-dependent kinases. Cyclin A, the first cyclin ever cloned, is thought to be an essential component of the cell-cycle engine. Mammalian cells encode two A-type cyclins, testis-specific cyclin A1 and ubiquitously expressed cyclin A2. Here, we tested the requirement for cyclin A function using conditional knockout mice lacking both A-type cyclins. We found that acute ablation of cyclin A in fibroblasts did not affect cell proliferation, but led to prolonged expression of another cyclin, cyclin E, across the cell cycle. However, combined ablation of all A- and E-type cyclins extinguished cell division. In contrast, cyclin A function was essential for cell-cycle progression of hematopoietic and embryonic stem cells. Expression of cyclin A is particularly high in these compartments, which might render stem cells dependent on cyclin A, whereas in fibroblasts cyclins A and E play redundant roles in cell proliferation.

MeSH Terms
Animals Cyclin A/genetics,metabolism Cyclin E/genetics,metabolism Embryo, Mammalian/cytology Embryonic Stem Cells/metabolism Fibroblasts/metabolism Hematopoietic Stem Cells/metabolism Mice Mice, Knockout
Chemicals
Cyclin A Cyclin E
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Kalaszczynska Ilona
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Geng Yan
Iino Tadafumi
Mizuno Shin-ichi
Choi Yoon
Kondratiuk Ilona
Silver Daniel P
Wolgemuth Debra J
Akashi Koichi
Sicinski Piotr
References (47)
47 references, click to expand
  1. A distinct cyclin A is expressed in germ cells in the mouse.
    Development. 1996 Jan;122(1):53-64 PMID: 8565853
  2. Kinase-independent function of cyclin E.
    Mol Cell. 2007 Jan 12;25(1):127-39 PMID: 17218276
  3. The clam embryo protein cyclin A induces entry into M phase and the resumption of meiosis in Xenopus oocytes.
    Cell. 1986 Dec 26;47(6):861-70 PMID: 2946420
  4. Human cyclin A is required for mitosis until mid prophase.
    J Cell Biol. 1999 Oct 18;147(2):295-306 PMID: 10525536
  5. A clonogenic common myeloid progenitor that gives rise to all myeloid lineages.
    Nature. 2000 Mar 9;404(6774):193-7 PMID: 10724173
  6. Human cyclin A is adenovirus E1A-associated protein p60 and behaves differently from cyclin B.
    Nature. 1990 Aug 23;346(6286):760-3 PMID: 2143810
  7. Delayed early embryonic lethality following disruption of the murine cyclin A2 gene.
    Nat Genet. 1997 Jan;15(1):83-6 PMID: 8988174
  8. p16INK4a induces an age-dependent decline in islet regenerative potential.
    Nature. 2006 Sep 28;443(7110):453-7 PMID: 16957737
  9. Characterization of a second human cyclin A that is highly expressed in testis and in several leukemic cell lines.
    Cancer Res. 1997 Mar 1;57(5):913-20 PMID: 9041194
  10. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation.
    Nature. 2003 Oct 30;425(6961):962-7 PMID: 14574365
  11. Cyclin E ablation in the mouse.
    Cell. 2003 Aug 22;114(4):431-43 PMID: 12941272
  12. Hybrid vigor, fetal overgrowth, and viability of mice derived by nuclear cloning and tetraploid embryo complementation.
    Proc Natl Acad Sci U S A. 2001 May 22;98(11):6209-14 PMID: 11331774
  13. Cyclin A but not cyclin D1 is essential for c-myc-modulated cell-cycle progression.
    J Cell Physiol. 2007 Jan;210(1):63-71 PMID: 17013808
  14. Cyclin: a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division.
    Cell. 1983 Jun;33(2):389-96 PMID: 6134587
  15. Cyclin A2 regulates nuclear-envelope breakdown and the nuclear accumulation of cyclin B1.
    Curr Biol. 2007 Jan 9;17(1):85-91 PMID: 17208191
  16. Cyclin A is required in S phase in normal epithelial cells.
    Biochem Biophys Res Commun. 1992 Feb 14;182(3):1144-54 PMID: 1531751
  17. Cyclin A1 protein shows haplo-insufficiency for normal fertility in male mice.
    Reproduction. 2004 Apr;127(4):503-11 PMID: 15047941
  18. Epiblast-restricted Cre expression in MORE mice: a tool to distinguish embryonic vs. extra-embryonic gene function.
    Genesis. 2000 Feb;26(2):113-5 PMID: 10686601
  19. Cyclin A1, the alternative A-type cyclin, contributes to G1/S cell cycle progression in somatic cells.
    Oncogene. 2005 Apr 14;24(16):2739-44 PMID: 15829981
  20. A detailed analysis of cyclin A accumulation at the G(1)/S border in normal and transformed cells.
    Exp Cell Res. 2000 Aug 25;259(1):86-95 PMID: 10942581
  21. Inducible gene targeting in mice.
    Science. 1995 Sep 8;269(5229):1427-9 PMID: 7660125
  22. Self-excising retroviral vectors encoding the Cre recombinase overcome Cre-mediated cellular toxicity.
    Mol Cell. 2001 Jul;8(1):233-43 PMID: 11511376
  23. Wnt signaling and stem cell control.
    Cell Res. 2008 May;18(5):523-7 PMID: 18392048
  24. Cyclin A is required for the onset of DNA replication in mammalian fibroblasts.
    Cell. 1991 Dec 20;67(6):1169-79 PMID: 1836977
  25. Cyclin A in cell cycle control and cancer.
    Cell Mol Life Sci. 2002 Aug;59(8):1317-26 PMID: 12363035
  26. Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a.
    Nature. 2006 Sep 28;443(7110):421-6 PMID: 16957735
  27. Cyclin A is destroyed in prometaphase and can delay chromosome alignment and anaphase.
    J Cell Biol. 2001 Apr 2;153(1):121-36 PMID: 11285279
  28. Cyclin A2 induces cardiac regeneration after myocardial infarction and prevents heart failure.
    Circ Res. 2007 Jun 22;100(12):1741-8 PMID: 17495221
  29. The roles of Drosophila cyclins A and B in mitotic control.
    Cell. 1990 May 4;61(3):535-47 PMID: 2139805
  30. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells.
    Nature. 2003 May 15;423(6937):302-5 PMID: 12714971
  31. The purification and characterization of fetal liver hematopoietic stem cells.
    Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10302-6 PMID: 7479772
  32. Cyclin-dependent kinases and cell-cycle transitions: does one fit all?
    Nat Rev Mol Cell Biol. 2008 Nov;9(11):910-6 PMID: 18813291
  33. Expression and function of Drosophila cyclin A during embryonic cell cycle progression.
    Cell. 1989 Mar 24;56(6):957-68 PMID: 2564316
  34. Whole-genome analysis of animal A- and B-type cyclins.
    Genome Biol. 2002;3(12):RESEARCH0070 PMID: 12537559
  35. Extracellular ATP induces anchorage-independent expression of cyclin A and rescues the transformed phenotype of a ras-resistant mutant cell line.
    J Biol Chem. 1997 Jan 31;272(5):3103-8 PMID: 9006962
  36. Cyclin A1 is required for meiosis in the male mouse.
    Nat Genet. 1998 Dec;20(4):377-80 PMID: 9843212
  37. Mouse development and cell proliferation in the absence of D-cyclins.
    Cell. 2004 Aug 20;118(4):477-91 PMID: 15315760
  38. Anaphase-promoting complex/cyclosome-dependent proteolysis of human cyclin A starts at the beginning of mitosis and is not subject to the spindle assembly checkpoint.
    J Cell Biol. 2001 Apr 2;153(1):137-48 PMID: 11285280
  39. Living with or without cyclins and cyclin-dependent kinases.
    Genes Dev. 2004 Nov 15;18(22):2699-711 PMID: 15545627
  40. C/EBPalpha is required for proteolytic cleavage of cyclin A by calpain 3 in myeloid precursor cells.
    J Biol Chem. 2002 Sep 13;277(37):33848-56 PMID: 12105198
  41. Accumulation of cyclin E is not a prerequisite for passage through the restriction point.
    Mol Cell Biol. 2001 May;21(9):3256-65 PMID: 11287628
  42. Cyclins E1 and E2 are required for endoreplication in placental trophoblast giant cells.
    EMBO J. 2003 Sep 15;22(18):4794-803 PMID: 12970191
  43. Cyclin A is required at two points in the human cell cycle.
    EMBO J. 1992 Mar;11(3):961-71 PMID: 1312467
  44. Differential modulation of cyclin gene expression by MYC.
    Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3685-9 PMID: 8386381
  45. A link between cyclin A expression and adhesion-dependent cell cycle progression.
    Science. 1993 Dec 3;262(5139):1572-5 PMID: 8248807
  46. Cyclin A links c-Myc to adhesion-independent cell proliferation.
    J Biol Chem. 1995 Jul 7;270(27):15923-5 PMID: 7608142
  47. Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing.
    Nature. 2006 Sep 28;443(7110):448-52 PMID: 16957738
Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2009.04.062
Published
2009-07-23
Epub
2009-00-09
Pages
352-65
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2745999
Subset
IM
Grants
NICHD NIH HHS · R01 HD034915 · United States
NICHD NIH HHS · R01HD034915 · United States
NCI NIH HHS · R01CA108950 · United States
NCI NIH HHS · R01 CA108950 · United States
NCI NIH HHS · R01 CA132740-01 · United States
NCI NIH HHS · R01 CA132740 · United States
NCI NIH HHS · R01CA132740 · United States
External Links
PubMed source DOI: 10.1016/j.cell.2009.04.062 PMC Full Text View journal details
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