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PMID: 17015432 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Control of cellular senescence by CPEB.

Genes & development ·Vol. 20 ·No. 19 ·2006-10-01 ·Pages 2701-12

Groisman I, Ivshina M, Marin V, Kennedy NJ, Davis RJ, Richter JD

Abstract

Cytoplasmic polyadenylation element-binding protein (CPEB) is a sequence-specific RNA-binding protein that promotes polyadenylation-induced translation. While a CPEB knockout (KO) mouse is sterile but overtly normal, embryo fibroblasts derived from this mouse (MEFs) do not enter senescence in culture as do wild-type MEFs, but instead are immortal. Exogenous CPEB restores senescence in the KO MEFs and also induces precocious senescence in wild-type MEFs. CPEB cannot stimulate senescence in MEFs lacking the tumor suppressors p53, p19ARF, or p16(INK4A); however, the mRNAs encoding these proteins are unlikely targets of CPEB since their expression is the same in wild-type and KO MEFs. Conversely, Ras cannot induce senescence in MEFs lacking CPEB, suggesting that it may lie upstream of CPEB. One target of CPEB regulation is myc mRNA, whose unregulated translation in the KO MEFs may cause them to bypass senescence. Thus, CPEB appears to act as a translational repressor protein to control myc translation and resulting cellular senescence.

MeSH Terms
Animals Blotting, Western/methods Cell Cycle/drug effects,physiology Cell Cycle Proteins/metabolism Cells, Cultured Cellular Senescence/drug effects,genetics,physiology Cyclin-Dependent Kinase Inhibitor p16/genetics,metabolism Fibroblasts/cytology,drug effects,metabolism Male Mice Mice, Knockout Phosphorylation/drug effects Protein Binding/drug effects Protein Biosynthesis/drug effects Proto-Oncogene Proteins c-myc/genetics,metabolism RNA, Messenger/genetics,metabolism RNA-Binding Proteins/genetics,pharmacology,physiology Tumor Suppressor Protein p14ARF/genetics,metabolism Tumor Suppressor Protein p53/genetics,metabolism mRNA Cleavage and Polyadenylation Factors/genetics,metabolism
Chemicals
CPEB protein, mouse Cdkn2a protein, mouse Cell Cycle Proteins Cyclin-Dependent Kinase Inhibitor p16 Proto-Oncogene Proteins c-myc RNA, Messenger RNA-Binding Proteins Tumor Suppressor Protein p14ARF Tumor Suppressor Protein p53 mRNA Cleavage and Polyadenylation Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Groisman Irina
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Ivshina Maria
Marin Veronica
Kennedy Norman J
Davis Roger J
Richter Joel D
References (53)
53 references, click to expand
  1. Cell-cycle control of c-myc but not c-ras expression is lost following chemical transformation.
    Cell. 1984 Feb;36(2):241-7 PMID: 6692471
  2. Differential mRNA translation and meiotic progression require Cdc2-mediated CPEB destruction.
    EMBO J. 2002 Apr 2;21(7):1833-44 PMID: 11927567
  3. Regulation of cell cycle duration by c-myc levels.
    Oncogene. 1989 Jun;4(6):773-87 PMID: 2660073
  4. Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line.
    Nucleic Acids Res. 1990 Jun 25;18(12):3587-96 PMID: 2194165
  5. Production of high-titer helper-free retroviruses by transient transfection.
    Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8392-6 PMID: 7690960
  6. CPEB is a specificity factor that mediates cytoplasmic polyadenylation during Xenopus oocyte maturation.
    Cell. 1994 Nov 18;79(4):617-27 PMID: 7954828
  7. Biological assays for Ras transformation.
    Methods Enzymol. 1995;255:395-412 PMID: 8524126
  8. A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
    Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9363-7 PMID: 7568133
  9. Mouse cytoplasmic polyadenylylation element binding protein: an evolutionarily conserved protein that interacts with the cytoplasmic polyadenylylation elements of c-mos mRNA.
    Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14602-7 PMID: 8962099
  10. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a.
    Cell. 1997 Mar 7;88(5):593-602 PMID: 9054499
  11. Specificity of RNA binding by CPEB: requirement for RNA recognition motifs and a novel zinc finger.
    Mol Cell Biol. 1998 Feb;18(2):685-93 PMID: 9447964
  12. C-Myc 5' untranslated region contains an internal ribosome entry segment.
    Oncogene. 1998 Jan 22;16(3):423-8 PMID: 9467968
  13. Contributions of Myc to tumorigenesis.
    Biochim Biophys Acta. 2002 Mar 14;1602(1):61-71 PMID: 11960695
  14. Translational control of the embryonic cell cycle.
    Cell. 2002 May 17;109(4):473-83 PMID: 12086604
  15. Dissolution of the maskin-eIF4E complex by cytoplasmic polyadenylation and poly(A)-binding protein controls cyclin B1 mRNA translation and oocyte maturation.
    EMBO J. 2002 Jul 15;21(14):3852-62 PMID: 12110596
  16. Cancer and ageing: rival demons?
    Nat Rev Cancer. 2003 May;3(5):339-49 PMID: 12724732
  17. Decapping and decay of messenger RNA occur in cytoplasmic processing bodies.
    Science. 2003 May 2;300(5620):805-8 PMID: 12730603
  18. Regulated CPEB phosphorylation during meiotic progression suggests a mechanism for temporal control of maternal mRNA translation.
    Genes Dev. 2003 Jun 15;17(12):1457-62 PMID: 12815066
  19. Immunoaffinity purification of mammalian protein complexes.
    Methods Enzymol. 2003;370:430-44 PMID: 14712665
  20. Principles of tumor suppression.
    Cell. 2004 Jan 23;116(2):235-46 PMID: 14744434
  21. Mammalian GLD-2 homologs are poly(A) polymerases.
    Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4407-12 PMID: 15070731
  22. The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis.
    Nat Med. 2004 May;10(5):484-6 PMID: 15098029
  23. Selective modulation of some forms of schaffer collateral-CA1 synaptic plasticity in mice with a disruption of the CPEB-1 gene.
    Learn Mem. 2004 May-Jun;11(3):318-27 PMID: 15169862
  24. The many roles of c-Myc in apoptosis.
    Annu Rev Physiol. 1998;60:575-600 PMID: 9558477
  25. CPEB-mediated cytoplasmic polyadenylation and the regulation of experience-dependent translation of alpha-CaMKII mRNA at synapses.
    Neuron. 1998 Nov;21(5):1129-39 PMID: 9856468
  26. c-Myc regulates cyclin D-Cdk4 and -Cdk6 activity but affects cell cycle progression at multiple independent points.
    Mol Cell Biol. 1999 Jul;19(7):4672-83 PMID: 10373516
  27. Living with or without cyclins and cyclin-dependent kinases.
    Genes Dev. 2004 Nov 15;18(22):2699-711 PMID: 15545627
  28. Symplekin and xGLD-2 are required for CPEB-mediated cytoplasmic polyadenylation.
    Cell. 2004 Nov 24;119(5):641-51 PMID: 15550246
  29. Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms.
    Genes Dev. 2005 Jan 1;19(1):104-13 PMID: 15630022
  30. Regulation of cap-dependent translation by eIF4E inhibitory proteins.
    Nature. 2005 Feb 3;433(7025):477-80 PMID: 15690031
  31. The translational regulator CPEB1 provides a link between dcp1 bodies and stress granules.
    J Cell Sci. 2005 Mar 1;118(Pt 5):981-92 PMID: 15731006
  32. The signals and pathways activating cellular senescence.
    Int J Biochem Cell Biol. 2005 May;37(5):961-76 PMID: 15743671
  33. Tumour biology: senescence in premalignant tumours.
    Nature. 2005 Aug 4;436(7051):642 PMID: 16079833
  34. Oncogene-induced senescence as an initial barrier in lymphoma development.
    Nature. 2005 Aug 4;436(7051):660-5 PMID: 16079837
  35. BRAFE600-associated senescence-like cell cycle arrest of human naevi.
    Nature. 2005 Aug 4;436(7051):720-4 PMID: 16079850
  36. Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis.
    Nature. 2005 Aug 4;436(7051):725-30 PMID: 16079851
  37. Differential phosphorylation controls Maskin association with eukaryotic translation initiation factor 4E and localization on the mitotic apparatus.
    Mol Cell Biol. 2005 Sep;25(17):7605-15 PMID: 16107707
  38. The thorny path linking cellular senescence to organismal aging.
    Mech Ageing Dev. 2005 Oct;126(10):1040-5 PMID: 16153470
  39. General translational repression by activators of mRNA decapping.
    Cell. 2005 Sep 23;122(6):875-86 PMID: 16179257
  40. Movement of eukaryotic mRNAs between polysomes and cytoplasmic processing bodies.
    Science. 2005 Oct 21;310(5747):486-9 PMID: 16141371
  41. Mammalian cyclin-dependent kinases.
    Trends Biochem Sci. 2005 Nov;30(11):630-41 PMID: 16236519
  42. Reduced extinction of hippocampal-dependent memories in CPEB knockout mice.
    Learn Mem. 2006 Jan-Feb;13(1):4-7 PMID: 16452649
  43. Translational control by neuroguidin, a eukaryotic initiation factor 4E and CPEB binding protein.
    Mol Cell Biol. 2006 Jun;26(11):4277-87 PMID: 16705177
  44. Maskin is a CPEB-associated factor that transiently interacts with elF-4E.
    Mol Cell. 1999 Dec;4(6):1017-27 PMID: 10635326
  45. Analysis of the c-myc IRES; a potential role for cell-type specific trans-acting factors and the nuclear compartment.
    Nucleic Acids Res. 2000 Feb 1;28(3):687-94 PMID: 10637319
  46. Phosphorylation of CPE binding factor by Eg2 regulates translation of c-mos mRNA.
    Nature. 2000 Mar 16;404(6775):302-7 PMID: 10749216
  47. CPEB, maskin, and cyclin B1 mRNA at the mitotic apparatus: implications for local translational control of cell division.
    Cell. 2000 Oct 27;103(3):435-47 PMID: 11081630
  48. Targeted disruption of the three Rb-related genes leads to loss of G(1) control and immortalization.
    Genes Dev. 2000 Dec 1;14(23):3037-50 PMID: 11114892
  49. Escape from premature senescence is not sufficient for oncogenic transformation by Ras.
    Nat Cell Biol. 2001 Feb;3(2):198-203 PMID: 11175753
  50. Loss of p16Ink4a with retention of p19Arf predisposes mice to tumorigenesis.
    Nature. 2001 Sep 6;413(6851):86-91 PMID: 11544531
  51. Germ cell differentiation and synaptonemal complex formation are disrupted in CPEB knockout mice.
    Dev Cell. 2001 Aug;1(2):201-13 PMID: 11702780
  52. A conserved role of a DEAD box helicase in mRNA masking.
    RNA. 2001 Dec;7(12):1728-42 PMID: 11780630
  53. Safe and efficient generation of recombinant retroviruses with amphotropic and ecotropic host ranges.
    Proc Natl Acad Sci U S A. 1988 Sep;85(17):6460-4 PMID: 3413107
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1438906
Published
2006-10-01
Pages
2701-12
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC1578696
Subset
IM
Grants
NIGMS NIH HHS · GM46779 · United States
NICHD NIH HHS · HD07312 · United States
NIDDK NIH HHS · P30 DK032520 · United States
NIDDK NIH HHS · DK32520 · United States
NICHD NIH HHS · T32 HD007312 · United States
NICHD NIH HHS · R01 HD037267 · United States
NIGMS NIH HHS · R01 GM046779 · United States
NICHD NIH HHS · R37 HD037267 · United States
External Links
PubMed source DOI: 10.1101/gad.1438906 PMC Full Text View journal details
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