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PMID: 8790367 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Cross talk between cell death and cell cycle progression: BCL-2 regulates NFAT-mediated activation.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 18 ·1996-09-03 ·Pages 9545-52

Linette GP, Li Y, Roth K, Korsmeyer SJ

Abstract

BCL-2-deficient T cells demonstrate accelerated cell cycle progression and increased apoptosis following activation. Increasing the levels of BCL-2 retarded the G0-->S transition, sustained the levels of cyclin-dependent kinase inhibitor p27Kip1, and repressed postactivation death. Proximal signal transduction events and immediate early gene transcription were unaffected. However, the transcription and synthesis of interleukin 2 and other delayed early cytokines were markedly attenuated by BCL-2. In contrast, a cysteine protease inhibitor that also blocks apoptosis had no substantial affect upon cytokine production. InterleUkin 2 expression requires several transcription factors of which nuclear translocation of NFAT (nuclear factor of activated T cells) and NFAT-mediated transactivation were impaired by BCL-2. Thus, select genetic aberrations in the apoptotic pathway reveal a cell autonomous coregulation of activation.

MeSH Terms
Apoptosis Cell Cycle Cell Cycle Proteins Cell Line Cyclin-Dependent Kinase Inhibitor p27 Cyclin-Dependent Kinases/antagonists & inhibitors Cysteine Proteinase Inhibitors/pharmacology DNA-Binding Proteins/metabolism Enzyme Inhibitors/metabolism Humans Interleukin-2/metabolism Lymphocyte Activation Microtubule-Associated Proteins/metabolism NFATC Transcription Factors Nuclear Proteins Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-bcl-2 Resting Phase, Cell Cycle S Phase Signal Transduction T-Lymphocytes/cytology,drug effects Transcription Factors/metabolism Tumor Suppressor Proteins
Chemicals
Cell Cycle Proteins Cysteine Proteinase Inhibitors DNA-Binding Proteins Enzyme Inhibitors Interleukin-2 Microtubule-Associated Proteins NFATC Transcription Factors Nuclear Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 Transcription Factors Tumor Suppressor Proteins Cyclin-Dependent Kinase Inhibitor p27 Cyclin-Dependent Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Linette G P
Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110, USA.
Li Y
Roth K
Korsmeyer S J
References (52)
52 references, click to expand
  1. Requirement for the coexpression of T3 and the T cell antigen receptor on a malignant human T cell line.
    J Exp Med. 1984 Nov 1;160(5):1284-99 PMID: 6208306
  2. Interleukin-2-mediated elimination of the p27Kip1 cyclin-dependent kinase inhibitor prevented by rapamycin.
    Nature. 1994 Dec 8;372(6506):570-3 PMID: 7990932
  3. The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining.
    Science. 1985 Sep 27;229(4720):1390-3 PMID: 3929382
  4. Nucleotide sequence of a t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a breakpoint-cluster region near a transcriptionally active locus on chromosome 18.
    Proc Natl Acad Sci U S A. 1985 Nov;82(21):7439-43 PMID: 2865728
  5. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells.
    Nature. 1988 Sep 29;335(6189):440-2 PMID: 3262202
  6. CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines.
    Proc Natl Acad Sci U S A. 1989 Feb;86(4):1333-7 PMID: 2465550
  7. bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation.
    Cell. 1989 Apr 7;57(1):79-88 PMID: 2649247
  8. G1 events and regulation of cell proliferation.
    Science. 1989 Nov 3;246(4930):603-8 PMID: 2683075
  9. Increases in tyrosine phosphorylation are detectable before phospholipase C activation after T cell receptor stimulation.
    J Immunol. 1990 Mar 1;144(5):1591-9 PMID: 1689750
  10. Deregulated Bcl-2 gene expression selectively prolongs survival of growth factor-deprived hemopoietic cell lines.
    J Immunol. 1990 May 1;144(9):3602-10 PMID: 2184193
  11. Single cell assay of a transcription factor reveals a threshold in transcription activated by signals emanating from the T-cell antigen receptor.
    Genes Dev. 1990 Oct;4(10):1823-34 PMID: 2123468
  12. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death.
    Nature. 1990 Nov 22;348(6299):334-6 PMID: 2250705
  13. The actions of cyclosporin A and FK506 suggest a novel step in the activation of T lymphocytes.
    EMBO J. 1990 Dec;9(13):4425-33 PMID: 1702384
  14. Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14; 18).
    Nature. 1991 Jan 17;349(6306):254-6 PMID: 1987477
  15. Analysis of cytokine gene expression during fetal thymic ontogeny using the polymerase chain reaction.
    J Immunol. 1991 Jul 15;147(2):554-60 PMID: 1649220
  16. Identification of DNA-replicating lymphocyte subsets using a new method to label the bromo-deoxyuridine incorporated into the DNA.
    J Immunol Methods. 1992 Mar 4;147(2):225-30 PMID: 1347775
  17. Induction of apoptosis in fibroblasts by c-myc protein.
    Cell. 1992 Apr 3;69(1):119-28 PMID: 1555236
  18. Social controls on cell survival and cell death.
    Nature. 1992 Apr 2;356(6368):397-400 PMID: 1557121
  19. FK-506- and CsA-sensitive activation of the interleukin-2 promoter by calcineurin.
    Nature. 1992 Jun 25;357(6380):692-4 PMID: 1377361
  20. Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation.
    Nature. 1992 Jun 25;357(6380):695-7 PMID: 1377362
  21. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.
    J Cell Biol. 1992 Nov;119(3):493-501 PMID: 1400587
  22. Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis.
    Nature. 1992 Sep 24;359(6393):288-94 PMID: 1406932
  23. Effects of an Rb mutation in the mouse.
    Nature. 1992 Sep 24;359(6393):295-300 PMID: 1406933
  24. E mu-bcl-2 transgene facilitates spontaneous transformation of early pre-B and immunoglobulin-secreting cells but not T cells.
    Oncogene. 1993 Jan;8(1):1-9 PMID: 8423986
  25. Continuous c-fos expression precedes programmed cell death in vivo.
    Nature. 1993 May 13;363(6425):166-9 PMID: 8483500
  26. Signal transduction events leading to T-cell lymphokine gene expression.
    Immunol Today. 1993 Jul;14(7):357-62 PMID: 8363726
  27. Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair.
    Cell. 1993 Oct 22;75(2):229-40 PMID: 8402909
  28. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.
    Cell. 1993 Nov 19;75(4):805-16 PMID: 8242751
  29. WAF1, a potential mediator of p53 tumor suppression.
    Cell. 1993 Nov 19;75(4):817-25 PMID: 8242752
  30. Growth factor starvation of bcl-2 overexpressing murine bone marrow cells induced refractoriness to IL-3 stimulation of proliferation.
    Oncogene. 1994 Apr;9(4):1117-22 PMID: 8134114
  31. Immunophilins in protein folding and immunosuppression.
    FASEB J. 1994 Apr 1;8(6):391-400 PMID: 7513288
  32. Inactivation of a Cdk2 inhibitor during interleukin 2-induced proliferation of human T lymphocytes.
    Mol Cell Biol. 1994 Jul;14(7):4889-901 PMID: 7516474
  33. Function and activation of NF-kappa B in the immune system.
    Annu Rev Immunol. 1994;12:141-79 PMID: 8011280
  34. Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals.
    Cell. 1994 Jul 15;78(1):59-66 PMID: 8033212
  35. p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21.
    Cell. 1994 Jul 15;78(1):67-74 PMID: 8033213
  36. Distinct signal transduction in mouse CD4+ and CD8+ splenic T cells after CD28 receptor ligation.
    J Immunol. 1995 Feb 1;154(3):985-97 PMID: 7822814
  37. Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice.
    Science. 1995 Mar 10;267(5203):1506-10 PMID: 7878471
  38. Bcl-2 is upregulated at the CD4+ CD8+ stage during positive selection and promotes thymocyte differentiation at several control points.
    Immunity. 1994 Jun;1(3):197-205 PMID: 7889408
  39. Three distinct IL-2 signaling pathways mediated by bcl-2, c-myc, and lck cooperate in hematopoietic cell proliferation.
    Cell. 1995 Apr 21;81(2):223-31 PMID: 7736574
  40. The retinoblastoma protein and cell cycle control.
    Cell. 1995 May 5;81(3):323-30 PMID: 7736585
  41. Inhibitors of mammalian G1 cyclin-dependent kinases.
    Genes Dev. 1995 May 15;9(10):1149-63 PMID: 7758941
  42. Bclx regulates the survival of double-positive thymocytes.
    Proc Natl Acad Sci U S A. 1995 May 23;92(11):4763-7 PMID: 7761398
  43. Peripheral T-cell lymphoma in lckpr-bcl-2 transgenic mice.
    Blood. 1995 Aug 15;86(4):1255-60 PMID: 7632929
  44. NFATc3, a lymphoid-specific NFATc family member that is calcium-regulated and exhibits distinct DNA binding specificity.
    J Biol Chem. 1995 Aug 25;270(34):19898-907 PMID: 7650004
  45. Regulation of cell division cycle progression by bcl-2 expression: a potential mechanism for inhibition of programmed cell death.
    J Exp Med. 1996 May 1;183(5):2219-26 PMID: 8642331
  46. Fas-induced activation of the cell death-related protease CPP32 Is inhibited by Bcl-2 and by ICE family protease inhibitors.
    J Biol Chem. 1996 Jul 12;271(28):16850-5 PMID: 8663439
  47. c-Myc-induced apoptosis in fibroblasts is inhibited by specific cytokines.
    EMBO J. 1994 Jul 15;13(14):3286-95 PMID: 8045259
  48. NF-ATp: a transcription factor required for the co-ordinate induction of several cytokine genes.
    Immunol Today. 1994 Jun;15(6):274-81 PMID: 8068174
  49. Deregulated expression of E2F-1 induces S-phase entry and leads to apoptosis.
    Mol Cell Biol. 1994 Dec;14(12):8166-73 PMID: 7969153
  50. Deregulated transcription factor E2F-1 expression leads to S-phase entry and p53-mediated apoptosis.
    Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10918-22 PMID: 7971984
  51. Signal transmission between the plasma membrane and nucleus of T lymphocytes.
    Annu Rev Biochem. 1994;63:1045-83 PMID: 7979236
  52. Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around JH on chromosome 14 and near a transcriptional unit on 18.
    Cell. 1985 Jul;41(3):899-906 PMID: 3924412
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.18.9545
Published
1996-09-03
Pages
9545-52
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC38465
Subset
IM
Grants
NCI NIH HHS · CA 49712 · United States
External Links
PubMed source DOI: 10.1073/pnas.93.18.9545 PMC Full Text View journal details
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