CAMP responsive element modulator: A critical regulator of cytokine production

Trends in Molecular Medicine

Volumn 19, Issue 4, 2013, Pages 262-269

  Rauen, Thomas ^a,b   Hedrich, Christian M ^a,c   Tenbrock, Klaus ^b   Tsokos, George C ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b RWTH AACHEN UNIVERSITY   (Germany)

^c UNIVERSITY HOSPITAL CARL GUSTAV CARUS   (Germany)

Author keywords

CREM; Cytokine; Epigenetics; Lymphocyte; SLE; Systemic lupus erythematosus; Transcription

Indexed keywords

ARALKYLAMINE ACETYLTRANSFERASE; CAMP RESPONSIVE ELEMENT MODULATOR; CYCLIC AMP; CYTOCHROME P450 17; CYTOSINE; DNA METHYLTRANSFERASE; FAS LIGAND; HISTONE DEACETYLASE; HISTONE DEACETYLASE 1; INTERLEUKIN 17; INTERLEUKIN 17F; INTERLEUKIN 2; MACROPHAGE INFLAMMATORY PROTEIN 1BETA; PROACROSIN; PROTAMINE; PROTEIN KINASE SYK; RHOB GUANINE NUCLEOTIDE BINDING PROTEIN; STEROL 14ALPHA DEMETHYLASE; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR NFAT; TYROSINE 3 MONOOXYGENASE; UNCLASSIFIED DRUG;

ACETYLATION; ANTIGEN PRESENTING CELL; AUTOIMMUNE DISEASE; AUTOIMMUNITY; CELL DIFFERENTIATION; CELL HOMING; CELL TYPE; CPG ISLAND; CYTOKINE PRODUCTION; DNA METHYLATION; DNA MODIFICATION; ENZYME ACTIVITY; EPIGENETICS; GENE LOCUS; GENE REPRESSION; GENETIC TRANSCRIPTION; HISTONE METHYLATION; HUMAN; IMMUNOMODULATION; IMMUNOPATHOGENESIS; NONHUMAN; PROMOTER REGION; PROTEIN CONFORMATION; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; SYSTEMIC LUPUS ERYTHEMATOSUS; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TRANSCRIPTION REGULATION;

ACETYLATION; ANIMALS; ANTIGEN-PRESENTING CELLS; CYCLIC AMP RESPONSE ELEMENT MODULATOR; CYTOKINES; DNA METHYLATION; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION; HISTONES; HUMANS; LUPUS ERYTHEMATOSUS, SYSTEMIC; PROMOTER REGIONS, GENETIC; SIGNAL TRANSDUCTION; T-LYMPHOCYTES;

EID: 84875846171     PISSN: 14714914     EISSN: 1471499X     Source Type: Journal    
DOI: 10.1016/j.molmed.2013.02.001     Document Type: Review

References (74)

1. Tsokos G.C. Systemic lupus erythematosus. N. Engl. J. Med. 2011, 365:2110-2121.
2. Tan W., et al. Association of PPP2CA polymorphisms with systemic lupus erythematosus susceptibility in multiple ethnic groups. Arthritis Rheum. 2011, 63:2755-2763.
3. Grammatikos A.P., Tsokos G.C. Immunodeficiency and autoimmunity: lessons from systemic lupus erythematosus. Trends Mol. Med. 2012, 18:101-108.
4. Ramantani G., et al. Expanding the phenotypic spectrum of lupus erythematosus in Aicardi-Goutieres syndrome. Arthritis Rheum. 2010, 62:1469-1477.
5. Moser K.L., et al. Recent insights into the genetic basis of systemic lupus erythematosus. Genes Immun. 2009, 10:373-379.
6. Kavanagh D., et al. New roles for the major human 3'-5' exonuclease TREX1 in human disease. Cell Cycle 2008, 7:1718-1725.
7. Truedsson L., et al. Complement deficiencies and systemic lupus erythematosus. Autoimmunity 2007, 40:560-566.
8. Ramos P.S., et al. Genetic analyses of interferon pathway-related genes reveal multiple new loci associated with systemic lupus erythematosus. Arthritis Rheum. 2011, 63:2049-2057.
9. Ramos P.S., et al. A comprehensive analysis of shared loci between systemic lupus erythematosus (SLE) and sixteen autoimmune diseases reveals limited genetic overlap. PLoS Genet. 2011, 7:e1002406.
10. Hedrich C.M., Tsokos G.C. Epigenetic mechanisms in systemic lupus erythematosus and other autoimmune diseases. Trends Mol. Med. 2011, 17:714-724.
11. + T cells. J. Autoimmun. 2010, 35:58-69.
12. + T cells. Lupus 2011, 20:1365-1371.
13. Strickland F.M., Richardson B.C. Epigenetics in human autoimmunity. epigenetics in autoimmunity - DNA methylation in systemic lupus erythematosus and beyond. Autoimmunity 2008, 41:278-286.
14. Renaudineau Y., Youinou P. Epigenetics and autoimmunity, with special emphasis on methylation. Keio J. Med. 2011, 60:10-16.
15. Sunahori K., et al. Promoter hypomethylation results in increased expression of protein phosphatase 2A in T cells from patients with systemic lupus erythematosus. J. Immunol. 2011, 186:4508-4517.
16. Barcellos L.F., et al. High-density SNP screening of the major histocompatibility complex in systemic lupus erythematosus demonstrates strong evidence for independent susceptibility regions. PLoS Genet. 2009, 5:e1000696.
17. Monaco L., et al. Specialized rules of gene transcription in male germ cells: the CREM paradigm. Int. J. Androl. 2004, 27:322-327.
18. de Groot R.P., et al. Multiple and cooperative phosphorylation events regulate the CREM activator function. EMBO J. 1993, 12:3903-3911.
19. Juang Y.T., et al. Systemic lupus erythematosus serum IgG increases CREM binding to the IL-2 promoter and suppresses IL-2 production through CaMKIV. J. Clin. Invest. 2005, 115:996-1005.
20. Foulkes N.S., et al. CREM gene: use of alternative DNA-binding domains generates multiple antagonists of cAMP-induced transcription. Cell 1991, 64:739-749.
21. Montminy M.R., Bilezikjian L.M. Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene. Nature 1987, 328:175-178.
22. Solomou E.E., et al. Molecular basis of deficient IL-2 production in T cells from patients with systemic lupus erythematosus. J. Immunol. 2001, 166:4216-4222.
23. Kyttaris V.C., et al. CAMP response element modulator α expression in patients with systemic lupus erythematosus. Lupus 2006, 15:840-844.
24. Juang Y.T., et al. Transcriptional activation of the cAMP-responsive modulator promoter in human T cells is regulated by protein phosphatase 2A-mediated dephosphorylation of SP-1 and reflects disease activity in patients with systemic lupus erythematosus. J. Biol. Chem. 2011, 286:1795-1801.
25. Foulkes N.S., et al. Developmental switch of CREM function during spermatogenesis: from antagonist to activator. Nature 1992, 355:80-84.
26. Masquilier D., et al. Human CREM gene: evolutionary conservation, chromosomal localization, and inducibility of the transcript. Cell Growth Differ. 1993, 4:931-937.
27. Higai K., et al. Prolonged high glucose suppresses phorbol 12-myristate 13-acetate and ionomycin-induced interleukin-2 mRNA expression in Jurkat cells. Biochim. Biophys. Acta 2009, 1790:8-15.
28. Molina C.A., et al. Inducibility and negative autoregulation of CREM: an alternative promoter directs the expression of ICER, an early response repressor. Cell 1993, 75:875-886.
29. Vicart A., et al. Increased chromatin association of Sp1 in interphase cells by PP2A-mediated dephosphorylations. J. Mol. Biol. 2006, 364:897-908.
30. Katsiari C.G., et al. Protein phosphatase 2A is a negative regulator of IL-2 production in patients with systemic lupus erythematosus. J. Clin. Invest. 2005, 115:3193-3204.
31. Moulton V.R., et al. Estrogen upregulates cyclic AMP response element modulator α expression and downregulates interleukin-2 production by human T lymphocytes. Mol. Med. 2012, 18:370-378.
32. Rauen T., et al. A novel intronic cAMP response element modulator (CREM) promoter is regulated by activator protein-1 (AP-1) and accounts for altered activation-induced CREM expression in T cells from patients with systemic lupus erythematosus. J. Biol. Chem. 2011, 286:32366-32372.
33. Kyttaris V.C., et al. Cyclic adenosine 5'-monophosphate response element modulator is responsible for the decreased expression of c-fos and activator protein-1 binding in T cells from patients with systemic lupus erythematosus. J. Immunol. 2004, 173:3557-3563.
34. Hedrich C.M., et al. cAMP response element modulator α controls IL2 and IL17A expression during CD4 lineage commitment and subset distribution in lupus. Proc. Natl. Acad. Sci. U.S.A. 2012, 109:16606-16611.
35. Broecker S., et al. Combined use of liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and high performance liquid chromatography with photodiode array detector (HPLC-DAD) in systematic toxicological analysis. Forensic Sci. Int. 2011, 212:215-226.
36. Bodor J., Habener J.F. Role of transcriptional repressor ICER in cyclic AMP-mediated attenuation of cytokine gene expression in human thymocytes. J. Biol. Chem. 1998, 273:9544-9551.
37. Bodor J., et al. Suppression of T cell function: a potential role for transcriptional repressor ICER. J. Leukoc. Biol. 2000, 67:774-779.
38. 2+, pCREB, and ICER. Naturwissenschaften 1996, 83:535-543.
39. Sallusto F., et al. Switch in chemokine receptor expression upon TCR stimulation reveals novel homing potential for recently activated T cells. Eur. J. Immunol. 1999, 29:2037-2045.
40. Tenbrock K., et al. Antisense cyclic adenosine 5'-monophosphate response element modulator up-regulates IL-2 in T cells from patients with systemic lupus erythematosus. J. Immunol. 2002, 169:4147-4152.
41. Tenbrock K., et al. The cyclic adenosine 5'-monophosphate response element modulator suppresses IL-2 production in stimulated T cells by a chromatin-dependent mechanism. J. Immunol. 2003, 170:2971-2976.
42. Hedrich C.M., et al. cAMP-responsive element modulator (CREM)α protein signaling mediates epigenetic remodeling of the human interleukin-2 gene: implications in systemic lupus erythematosus. J. Biol. Chem. 2011, 286:43429-43436.
43. Asahara H., et al. Chromatin-dependent cooperativity between constitutive and inducible activation domains in CREB. Mol. Cell. Biol. 2001, 21:7892-7900.
44. Rauen T., et al. cAMP-responsive element modulator (CREM)α protein induces interleukin 17A expression and mediates epigenetic alterations at the interleukin-17A gene locus in patients with systemic lupus erythematosus. J. Biol. Chem. 2011, 286:43437-43446.
45. Gaffen S.L. Recent advances in the IL-17 cytokine family. Curr. Opin. Immunol. 2011, 23:613-619.
46. Nistala K., Wedderburn L.R. Th17 and regulatory T cells: rebalancing pro- and anti-inflammatory forces in autoimmune arthritis. Rheumatology 2009, 48:602-606.
47. Zepp J., et al. IL-17 receptor signaling and T helper 17-mediated autoimmune demyelinating disease. Trends Immunol. 2011, 32:232-239.
48. Hundorfean G., et al. Functional relevance of T helper 17 (Th17) cells and the IL-17 cytokine family in inflammatory bowel disease. Inflamm. Bowel Dis. 2012, 18:180-186.
49. Crispin J.C., Tsokos G.C. IL-17 in systemic lupus erythematosus. J. Biomed. Biotechnol. 2010, 2010:943254.
50. Rajkovic M., et al. Functional cooperation between CREM and GCNF directs gene expression in haploid male germ cells. Nucleic Acids Res. 2010, 38:2268-2278.
51. Hedrich C.M., et al. cAMP-responsive element modulator α (CREMα) suppresses IL-17F protein expression in T lymphocytes from patients with systemic lupus erythematosus (SLE). J. Biol. Chem. 2012, 287:4715-4725.
52. Lippe R., et al. CREMα overexpression decreases IL-2 production, induces a TH17 phenotype and accelerates autoimmunity. J. Mol. Cell Biol. 2012, 4:121-123.
53. Tenbrock K., et al. The cyclic AMP response element modulator regulates transcription of the TCR ζ-chain. J. Immunol. 2005, 175:5975-5980.
54. Ghosh D., et al. CREMα suppresses spleen tyrosine kinase expression in normal but not systemic lupus erythematosus T cells. Arthritis Rheum. 2012, 64:799-807.
55. Gilchrist M., et al. Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4. Nature 2006, 441:173-178.
56. Ahlmann M., et al. The cyclic AMP response element modulator α suppresses CD86 expression and APC function. J. Immunol. 2009, 182:4167-4174.
57. Gerl V., et al. Blood dendritic cells in systemic lupus erythematosus exhibit altered activation state and chemokine receptor function. Ann. Rheum. Dis. 2010, 69:1370-1377.
58. Nantel F., et al. Spermiogenesis deficiency and germ-cell apoptosis in CREM-mutant mice. Nature 1996, 380:159-162.
59. Tenbrock K., Tsokos G.C. Transcriptional regulation of interleukin 2 in SLE T cells. Int. Rev. Immunol. 2004, 23:333-345.
60. Bodor J., et al. Differential inducibility of the transcriptional repressor ICER and its role in modulation of Fas ligand expression in T and NK lymphocytes. Eur. J. Immunol. 2002, 32:203-212.
61. Misund K., et al. Inducible cAMP early repressor splice variants ICER I and IIγ both repress transcription of c-fos and chromogranin A. J. Cell. Biochem. 2007, 101:1532-1544.
62. Vaeth M., et al. Regulatory T cells facilitate the nuclear accumulation of inducible cAMP early repressor (ICER) and suppress nuclear factor of activated T cell c1 (NFATc1). Proc. Natl. Acad. Sci. U.S.A. 2011, 108:2480-2485.
63. Barabitskaja O., et al. Suppression of MIP-1β transcription in human T cells is regulated by inducible cAMP early repressor (ICER). J. Leukoc. Biol. 2006, 79:378-387.
64. Zhou Y., et al. cAMP-response element modulator τ is a positive regulator of testis angiotensin converting enzyme transcription. Proc. Natl. Acad. Sci. U.S.A. 1996, 93:12262-12266.
65. Nagamori I., et al. Transcription factors, cAMP-responsive element modulator (CREM) and Tisp40, act in concert in postmeiotic transcriptional regulation. J. Biol. Chem. 2006, 281:15073-15081.
66. Foulkes N.S., et al. Rhythmic transcription: the molecular basis of circadian melatonin synthesis. Biol. Cell 1997, 89:487-494.
67. Tinti C., et al. Inducible cAMP early repressor can modulate tyrosine hydroxylase gene expression after stimulation of cAMP synthesis. J. Biol. Chem. 1996, 271:25375-25381.
68. Acimovic J., et al. CREM modulates the circadian expression of CYP51, HMGCR and cholesterogenesis in the liver. Biochem. Biophys. Res. Commun. 2008, 376:206-210.
69. Martianov I., et al. Cell-specific occupancy of an extended repertoire of CREM and CREB binding loci in male germ cells. BMC Genomics 2010, 11:530.
70. Muller F.U., et al. Heart-directed expression of a human cardiac isoform of cAMP-response element modulator in transgenic mice. J. Biol. Chem. 2005, 280:6906-6914.
71. Blendy J.A., et al. Severe impairment of spermatogenesis in mice lacking the CREM gene. Nature 1996, 380:162-165.
72. Tramer F., et al. cAMP-response element modulator- τ activates a distinct promoter element for the expression of the phospholipid hydroperoxide/sperm nucleus glutathione peroxidase gene. Biochem. J. 2004, 383:179-185.
73. Kosir R., et al. Circadian expression of steroidogenic cytochromes P450 in the mouse adrenal gland - involvement of cAMP-responsive element modulator in epigenetic regulation of Cyp17a1. FEBS J. 2012, 279:1584-1593.
74. Della Fazia M.A., et al. Stress-induced expression of transcriptional repressor ICER in the adrenal gland. FEBS Lett. 1998, 434:33-36.