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Testis, Epididymis and Technologies in the Year 2000 pp 107–128Cite as

Routes of Transcriptional Activation in the Testis: CREM and its Co-Activator ACT

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Part of the book series: Ernst Schering Research Foundation Workshop ((3368,volume 6))

Abstract

Coordinated gene expression programs govern the complex processes of cell growth and differentiation. The modulation of gene expression by specific signal transduction pathways enables cells to trigger the appropriate short- and long-term adaptation programs in response to environmental cues. Many transcription factors are final targets of specific transduction pathways. Factors of the CREB (cAMP-responsive element binding protein) family were originally identified as activators that respond directly to the cyclic AMP-dependent signaling pathway via phosphorylation by the protein kinase A (PKA) (Montminy 1997; Sassone-Corsi 1995). This family comprises a large number of proteins encoded by the CREB, CREM (cAMP-responsive element modulator) and ATF-1 (activating transcription factor 1) genes. Recently, it has become apparent that members of the CREB family play important roles in the nuclear responses to a variety of external signals. CREB and CREM have also been shown to function in many physiological systems, including memory and long-term potentiation (Silva et al. 1998), circadian rhythms (Foulkes et al. 1997), pituitary function (Struthers et al. 1991) and spermatogenesis (Sassone-Corsi 1998).

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References

  • Arany Z, Newsome D, Oldread E, Livingston DM, Eckner R (1995) A family of transcriptional adaptor proteins targeted by the El A oncoprotein. Nature 374: 81–84

    Article  PubMed  CAS  Google Scholar 

  • Arias J, Alberts AS, Brindle P, Claret FX, Smeal T, Karin M, Feramisco J, Montminy M (1994) Activation of cAMP and mitogen responsive genes relies on a common nuclear factor. Nature 370: 226–229

    Article  PubMed  CAS  Google Scholar 

  • Brindle P, Linke S, Montminy MR (1993) Protein-kinase A-dependent activator in transcription factor CREB reveals new role for CREM repressors. Nature 364: 821–824

    Article  PubMed  CAS  Google Scholar 

  • Chan KK, Tsui SK, Lee SM, Luk SC, Liew CC, Fung KP, Waye MM, Lee CY (1998) Molecular cloning and characterization of FHL2, a novel LIM domain protein preferentially expressed in human heart. Gene 210: 345–350

    Article  PubMed  CAS  Google Scholar 

  • Chrivia JC, Kwok RP, Lamb N, Hagiwara M, Montminy MR, Goodman RH (1993) Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 365: 855–859

    Article  PubMed  CAS  Google Scholar 

  • Cohen P (1997) The search for physiological substrates of MAP and SAP kinases in mammalian cells. Trends Cell Biol 7: 353–361

    Article  PubMed  CAS  Google Scholar 

  • Courey AJ, Tjian R (1988) Analysis of Spl in vivo reveals multiple transcriptional domains, including a novel glutamine-rich activation motif. Cell 55: 887–898

    Article  PubMed  CAS  Google Scholar 

  • Dawid IB, Breen JJ, Toyama R (1998) LIM domains: multiple roles as adapters and functional modifiers in protein interactions. Trends Genet 14: 156–162

    Article  PubMed  CAS  Google Scholar 

  • De Cesare D, Fimia GM, Sassone-Corsi P (1999) Signaling routes to CREM and CREB: plasticity in transcriptional activation. Trends Biochem Sci 24: 281–285

    Article  PubMed  Google Scholar 

  • De Cesare D, Jacquot S, Hanauer A, Sassone-Corsi P (1998) Rsk-2 activity is necessary for epidermal growth factor-induced phosphorylation of CREB protein and transcription of c-fos gene. Proc Natl Acad Sci USA 95: 12202–12207

    Article  PubMed  Google Scholar 

  • Groot R, Ballou LM, Sassone-Corsi P (1994) Positive regulation of the cAMP-responsive activator CREM by the p70 S6 kinase: an alternative route to mitogen-induced gene expression. Cell 79: 81–91

    Article  PubMed  Google Scholar 

  • Groot RP, den HJ, Vandenheede JR, Goris J, Sassone-Corsi P (1993) Multiple and cooperative phosphorylation events regulate the CREM activator function. EMBO J 12: 3903–3911

    PubMed  Google Scholar 

  • Deak M, Clifton AD, Lucocq LM, Alessi DR (1998) Mitogen-and stress-activated protein kinase-1 (MSKI) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. EMBO J 17: 4426–41

    Article  PubMed  CAS  Google Scholar 

  • Delmas V, van dHF, Mellstrom B, Jegou B, Sassone-Corsi P (1993) Induction of CREM activator proteins in spermatids: down-stream targets and implications for haploid germ cell differentiation. Mol Endocrinol 7: 1502–1514

    Article  PubMed  CAS  Google Scholar 

  • Eckner R, Ewen ME, Newsome D, Gerdes M, De CJ, Lawrence JB, Livingston DM (1994) Molecular cloning and functional analysis of the adenovirus ElA-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. Genes Dey 8: 869–884

    Article  CAS  Google Scholar 

  • Ferreri K, Gill G, Montminy M (1994) The cAMP-regulated transcription factor CREB interacts with a component of the TFIID complex. Proc Natl Acad Sci USA 91: 1210–1213

    Article  PubMed  CAS  Google Scholar 

  • Fimia GM, De Cesare D, Sassone-Corsi P (1998) Mechanisms of activation by CREB and CREM: phosphorylation, CBP, and a novel coactivator, ACT. Cold Spring Harb Symp Quant Biol 63: 631–642

    Google Scholar 

  • Fimia GM, De Cesare D, Sassone-Corsi P (1999) CBP-independent activation of CREM and CREB by the LIM-only protein ACT. Nature 398: 165–169

    Article  PubMed  CAS  Google Scholar 

  • Foulkes NS, Borjigin J, Snyder SH, Sassone-Corsi P (1997) Rhythmic transcription: the molecular basis of circadian melatonin synthesis. Trends Neurosci 20: 487–492

    Article  PubMed  CAS  Google Scholar 

  • Foulkes NS, Borrelli E, Sassone-Corsi P (1991) CREM gene: use of alternative DNA-binding domains generates multiple antagonists of cAMP-induced transcription. Cell 64: 739–749

    Article  PubMed  CAS  Google Scholar 

  • Foulkes NS, Mellstrom B, Benusiglio E, Sassone-Corsi P (1992) Developmental switch of CREM function during spermatogenesis: from antagonist to activator. Nature 355: 80–84

    Article  PubMed  CAS  Google Scholar 

  • Foulkes NS, Schiotter F, Pevet P, Sassone-Corsi P (1993) Pituitary hormone FSH directs the CREM functional switch during spermatogenesis. Nature 362: 264–267

    Article  PubMed  CAS  Google Scholar 

  • Genini M, Schwalbe P, Scholl FA, Remppis A, Mattei MG, Schafer BW (1997) Subtractive cloning and characterization of DRAL, a novel LIM-domain protein down-regulated in rhabdomyosarcoma. DNA Cell Biol 16: 433–442

    Article  PubMed  CAS  Google Scholar 

  • Ginty DD, Bonni A, Greenberg ME (1994) Nerve growth factor activates a Ras-dependent protein kinase that stimulates c-fos transcription via phosphorylation of CREB. Cell 77: 713–725

    Article  PubMed  Google Scholar 

  • Gonzalez GA, Montminy MR (1989) Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell 59: 675–680

    Article  PubMed  CAS  Google Scholar 

  • Hai TW, Liu F, Coukos WJ, Green MR (1989) Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers [published erratum appears in Genes Dev 1990 Apr; 4(4):682]. Genes Dev 3: 2083–2090

    Article  PubMed  CAS  Google Scholar 

  • Iordanov M, Bender K, Ade T, Schmid W, Sachsenmaier C, Engel K, Gaestel M, Rahmsdorf HJ, Herrlich P (1997) CREB is activated by UVC through a p38/HOG-1-dependent protein kinase. EMBO J 16: 1009–1022

    Article  PubMed  CAS  Google Scholar 

  • Jégou B (1993) The Sertoli-germ cell communication network in mammals. Int Rev Cytol 147: 25–96

    Article  PubMed  Google Scholar 

  • Kistler MK, Sassone-Corsi P, Kistler WS (1994) Identification of a functional cyclic adenosine 3’,5’-monophosphate response element in the 5’-flanking region of the gene for transition protein 1 (TP1), a basic chromosomal protein of mammalian spermatids. Biol Reprod 51: 1322–1329

    Article  PubMed  CAS  Google Scholar 

  • Kouzarides T (1999) Histone acetylases and deacetylases in cell proliferation. Curr Opin Genet Dev 9: 40–48

    Article  PubMed  CAS  Google Scholar 

  • Kwok RP, Lundblad JR, Chrivia JC, Richards JP, Bachinger HP, Brennan RG, Roberts SG, Green MR, Goodman RH (1994) Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature 370: 223–226

    Article  PubMed  CAS  Google Scholar 

  • Lalli E, Sassone-Corsi P (1994) Signal transduction and gene regulation: the nuclear response to cAMP. J Biol Chem 269: 17359–17362

    PubMed  CAS  Google Scholar 

  • Lamas M, Sassone-Corsi P (1997) The dynamics of the transcriptional response to cyclic adenosine 3’,5’ -monophosphate: recurrent inducibility and refractory phase. Mol Endocrinol 11: 1415–1424

    Article  PubMed  CAS  Google Scholar 

  • Laoide BM, Foulkes NS, Schlotter F, Sassone-Corsi P (1993) The functional versatility of CREM is determined by its modular structure. EMBO J 12: 1179–1191

    PubMed  CAS  Google Scholar 

  • McKnight GS, Clegg CH, Uhler MD, Chrivia JC, Cadd GG, Correll LA, Otten AD (1988) Analysis of the cAMP-dependent protein kinase system using molecular genetic approaches. Recent Prog Horm Res 44: 307–335

    PubMed  CAS  Google Scholar 

  • Molina CA, Foulkes NS, Lalli E, Sassone-Corsi P (1993) Inducibility and negative autoregulation of CREM: an alternative promoter directs the expression of ICER, an early response repressor. Cell 75: 875–886

    Article  PubMed  CAS  Google Scholar 

  • Montminy M (1997) Transcriptional regulation by cyclic AMP. Annu Rev Biochem 66: 807–822

    Article  PubMed  CAS  Google Scholar 

  • Morgan MJ, Madgwick AJA (1996) Slim defines a novel family of LIM-proteins expressed in skeletal muscle. Biochem Biophys Res Commun 225: 632–638

    Article  PubMed  CAS  Google Scholar 

  • Morgan MJ, Madgwick AJA (1999) The fourth member of the FHL family of LIM proteins is expressed exclusively in the testis. Biochem Biophys Res Commun 255: 251–255

    Article  PubMed  CAS  Google Scholar 

  • Nakajima T, Uchida C, Anderson SF, Lee CG, Hurwitz J, Parvin JD, Montminy M (1997) RNA helicase A mediates association of CBP with RNA polymerase II. Cell 90: 1107–1112

    Article  PubMed  CAS  Google Scholar 

  • Nantel F, Monaco L, Foulkes NS, Masquilier D, Le MM, Henriksen K, Dierich A, Parvinen M, Sassone-Corsi P (1996) Spermiogenesis deficiency and germ-cell apoptosis in CREM-mutant mice. Nature 380: 159–162

    Article  PubMed  CAS  Google Scholar 

  • Radhakrishnan I, Perez-Alvarado GC, Parker D, Dyson HJ, Montminy MR, Wright PE (1997) Solution structure of the KIX domain of CBP bound to the transactivation domain of CREB: a model for activator:coactivator interactions. Cell 91: 741–752

    Article  PubMed  CAS  Google Scholar 

  • Rehfuss RP, Walton KM, Loriaux MM, Goodman RH (1991) The cAMP-regulated enhancer-binding protein ATF-1 activates transcription in response to cAMP-dependent protein kinase A. J Biol Chem 266: 18431–18434

    PubMed  CAS  Google Scholar 

  • Roesler WJ, Vandenbark GR, Hanson RW (1988) Cyclic AMP and the induction of eukaryotic gene transcription. J Biol Chem 263: 9063–9066

    PubMed  CAS  Google Scholar 

  • Rozman D, Fink M, Fimia GM, Sassone-Corsi P, Waterman MR (1999) cAMP/CREM-dependent regulation of cholesterogenic lanosterol 14-alpha demethylase (CYP51) in spermatids. Mol Endocrinol 13: 1951–1962.

    Google Scholar 

  • Sassone-Corsi P (1995) Transcription factors responsive to cAMP. Annu Rev Cell Dev Biol 11: 355–377

    Article  PubMed  CAS  Google Scholar 

  • Sassone-Corsi P (1997) Transcriptional checkpoints determining the fate of male germ cells. Cell 88: 163–166

    Article  PubMed  CAS  Google Scholar 

  • Sassone-Corsi P (1998) CREM: a master-switch governing male germ cell differentiation and apoptotis. Sem Cell Dev Biol 9: 475–482

    Article  CAS  Google Scholar 

  • Sassone-Corsi P, Visvader J, Ferland L, Mellon PL, Verma IM (1988) Induction of proto-oncogene fos transcription through the adenylate cyclase pathway: characterization of a cAMP-responsive element. Genes Dev 2: 1529–1538

    Article  PubMed  CAS  Google Scholar 

  • Schmeichel KL, Beckerle MC (1994) The LIM domain is a modular protein-binding interface. Cell 79: 211–219

    Article  PubMed  CAS  Google Scholar 

  • Sheng M, Thompson MA, Greenberg ME (1991) CREB: a Ca2+-regulated transcription factor phosphorylated by calmodulin-dependent kinases. Science 252: 1427–1430

    Article  PubMed  CAS  Google Scholar 

  • Shikama N, Lyon J, La Thangue NB (1997) The p300/CBP family: integrating signals with transcription factors and chromatin. Trends Cell Biol 7: 230–236

    Article  CAS  Google Scholar 

  • Silva AJ, Kogan JH, Frankland PW, Kida S (1998) CREB and memory. Annu Rev Neurosci 21: 127–148

    Article  PubMed  CAS  Google Scholar 

  • Struthers RS, Vale WW, Arias C, Sawchenko PE, Montminy MR (1991) Somatotroph hypoplasia and dwarfism in transgenic mice expressing a non-phosphorylatable CREB mutant. Nature 350: 622–624

    Article  PubMed  CAS  Google Scholar 

  • Sun Z, Sassone-Corsi P, Means AR (1995) Calspermin gene transcription is regulated by two cyclic AMP response elements contained in an alternative promoter in the calmodulin kinase IV gene. Mol Cell Biol 15: 561–571

    PubMed  CAS  Google Scholar 

  • Tan Y, Rouse J, Zhang A, Cariati S, Cohen P, Comb MJ (1996) FGF and stress regulate CREB and ATF-1 via a pathway involving p38 MAP kinase and MAPKAP kinase-2. EMBO J 15: 4629–4642

    PubMed  CAS  Google Scholar 

  • Taniguchi Y, Furukawa T, Tun T, Han H, Honjo T (1998) LIM protein KyoT2 negatively regulates transcription by association with the RBP-J DNA-binding protein. Mol Cell Biol 18: 644–654

    PubMed  CAS  Google Scholar 

  • Williams T, Admon A, Luscher B, Tjian R (1988) Cloning and expression of AP-2, a cell-type-specific transcription factor that activates inducible enhancer elements. Genes Dev 2: 1557–1569

    Article  PubMed  CAS  Google Scholar 

  • Xing J, Ginty DD, Greenberg ME (1996) Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase. Science 273: 959–963

    Article  PubMed  CAS  Google Scholar 

  • Zhou Y, Sun Z, Means AR, Sassone CP, Bernstein KE (1996) cAMP-response element modulator tau is a positive regulator of testis angiotensin converting enzyme transcription. Proc Natl Acad Sci USA 93: 12262–12266

    Google Scholar 

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Authors
  1. D. De Cesare
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  2. G. M. Fimia
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  3. A. Morlon
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  4. P. Sassone-Corsi
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Editors and Affiliations

  1. GERM-INSERM U. 435, Université de Rennes, Campus de Beaulieu, 35042, Rennes, Bretagne, France

    B. Jégou  & C. Pineau  & 

  2. INSERM U. 369, Faculté de médicine Lyon-RTH Laennec, rue Guillaume Paradin, 69372, Lyon, Cedex 08, France

    J. Saez

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© 2000 Springer-Verlag Berlin Heidelberg

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De Cesare, D., Fimia, G.M., Morlon, A., Sassone-Corsi, P. (2000). Routes of Transcriptional Activation in the Testis: CREM and its Co-Activator ACT. In: Jégou, B., Pineau, C., Saez, J. (eds) Testis, Epididymis and Technologies in the Year 2000. Ernst Schering Research Foundation Workshop, vol 6. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-04050-8_8

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  • DOI: https://doi.org/10.1007/978-3-662-04050-8_8

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-04052-2

  • Online ISBN: 978-3-662-04050-8

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