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Gene Review

Crem  -  cAMP responsive element modulator

Mus musculus

Synonyms: ICER, ICERI, Inducible cAMP early repressor, cAMP-responsive element modulator
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Disease relevance of Crem


Psychiatry related information on Crem


High impact information on Crem


Biological context of Crem

  • Tax binds to enhancer-binding proteins including cAMP-responsive element-binding protein, cAMP-responsive element modulator, transcription factor NF-kappa B p50 and p67SRF, and associates with each enhancer DNA indirectly [7].
  • S-CREM shares with the other CREM proteins the basic DNA-binding and leucine-zipper dimerization domain [8].
  • Induction of CREM activator proteins in spermatids: down-stream targets and implications for haploid germ cell differentiation [9].
  • Phosphorylation of serine-117 turns CREM tau into a powerful activator [9].
  • The rise in CREM tau protein coincides with the transcriptional activation of several genes [9].

Anatomical context of Crem


Chemical compound and disease context of Crem


Associations of Crem with chemical compounds

  • We show that CREM tau is efficiently phosphorylated at a serine residue at position 117 by the protein kinase-A endogenous to germ cells, indicating that it constitutes a natural target of the adenylyl cyclase pathway during spermatogenesis [9].
  • Mice lacking the functional cAMP responsive element modulator (CREM) gene, a component of cAMP-mediated signal transduction, exhibit a specific arrest of round spermatid development although follicle stimulating hormone (FSH) and androgen secretion are not impaired [14].

Analytical, diagnostic and therapeutic context of Crem

  • In particular, we determined by RT-PCR that a switch from the expression of CREM repressors to CREM activators is present in postmeiotic germ cells in normospermic men [15].


  1. Novel cyclic adenosine 3',5'-monophosphate (cAMP) response element modulator theta isoforms expressed by two newly identified cAMP-responsive promoters active in the testis. Daniel, P.B., Rohrbach, L., Habener, J.F. Endocrinology (2000) [Pubmed]
  2. Cyclic AMP response element-binding protein is required for normal maternal nurturing behavior. Jin, S.H., Blendy, J.A., Thomas, S.A. Neuroscience (2005) [Pubmed]
  3. Abnormal sperm in mice with targeted deletion of the act (activator of cAMP-responsive element modulator in testis) gene. Kotaja, N., De Cesare, D., Macho, B., Monaco, L., Brancorsini, S., Goossens, E., Tournaye, H., Gansmuller, A., Sassone-Corsi, P. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. Gonadotropin-regulated testicular RNA helicase (GRTH/Ddx25) is essential for spermatid development and completion of spermatogenesis. Tsai-Morris, C.H., Sheng, Y., Lee, E., Lei, K.J., Dufau, M.L. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  5. The kinesin KIF17b and RNA-binding protein TB-RBP transport specific cAMP-responsive element modulator-regulated mRNAs in male germ cells. Chennathukuzhi, V., Morales, C.R., El-Alfy, M., Hecht, N.B. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  6. Transcriptional control of circadian hormone synthesis via the CREM feedback loop. Foulkes, N.S., Borjigin, J., Snyder, S.H., Sassone-Corsi, P. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  7. Tax protein of human T-cell leukemia virus type I binds to the ankyrin motifs of inhibitory factor kappa B and induces nuclear translocation of transcription factor NF-kappa B proteins for transcriptional activation. Hirai, H., Suzuki, T., Fujisawa, J., Inoue, J., Yoshida, M. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  8. Alternative usage of initiation codons in mRNA encoding the cAMP-responsive-element modulator generates regulators with opposite functions. Delmas, V., Laoide, B.M., Masquilier, D., de Groot, R.P., Foulkes, N.S., Sassone-Corsi, P. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  9. Induction of CREM activator proteins in spermatids: down-stream targets and implications for haploid germ cell differentiation. Delmas, V., van der Hoorn, F., Mellström, B., Jégou, B., Sassone-Corsi, P. Mol. Endocrinol. (1993) [Pubmed]
  10. Differential activation of viral and cellular promoters by human T-cell lymphotropic virus-1 tax and cAMP-responsive element modulator isoforms. Laurance, M.E., Kwok, R.P., Huang, M.S., Richards, J.P., Lundblad, J.R., Goodman, R.H. J. Biol. Chem. (1997) [Pubmed]
  11. Cloning and expression analysis of testis-specific cyclic 3', 5'-adenosine monophosphate-responsive element modulator activators in the nonhuman primate (Macaca fascicularis): comparison with other primate and rodent species. Behr, R., Hunt, N., Ivell, R., Wessels, J., Weinbauer, G.F. Biol. Reprod. (2000) [Pubmed]
  12. Identification of novel cAMP responsive element modulator (CREM) isoforms expressed by osteoblasts. Liu, F., Huang, Y.F., Kream, B.E. Calcif. Tissue Int. (2005) [Pubmed]
  13. Negative regulation of TLR responses by the neuropeptide CGRP is mediated by the transcriptional repressor ICER. Harzenetter, M.D., Novotny, A.R., Gais, P., Molina, C.A., Altmayr, F., Holzmann, B. J. Immunol. (2007) [Pubmed]
  14. Testicular cAMP responsive element modulator (CREM) protein is expressed in round spermatids but is absent or reduced in men with round spermatid maturation arrest. Weinbauer, G.F., Behr, R., Bergmann, M., Nieschlag, E. Mol. Hum. Reprod. (1998) [Pubmed]
  15. Cyclic adenosine 3',5'-monophosphate-responsive element modulator gene expression in germ cells of normo- and oligoazoospermic men. Peri, A., Krausz, C., Cioppi, F., Granchi, S., Forti, G., Francavilla, S., Serio, M. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
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