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cAMP responsive element modulator

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cAMP responsive element modulator is a protein that in humans is encoded by the CREM gene,[5][6][7] and it belongs to the cAMP-responsive element binding protein family. It has multiple isoforms, which act either as repressors or activators.[8] CREB family is important for in regulating transcription in response to various stresses, metabolic and developmental signals.[9] CREM transcription factors also play an important role in many physiological systems, such as cardiac function,[10] circadian rhythms,[11] locomotion and spermatogenesis.[12]

CREM
Identifiers
AliasesCREM, CREM-2, ICER, hCREM-2, cAMP responsive element modulator
External IDsOMIM: 123812; MGI: 88495; HomoloGene: 84591; GeneCards: CREM; OMA:CREM - orthologs
Orthologs
SpeciesHumanMouse
Entrez

1390

12916

Ensembl

ENSG00000095794

ENSMUSG00000063889

UniProt

Q03060

P27699

RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)Chr 10: 35.13 – 35.21 MbChr 18: 3.27 – 3.34 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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This gene encodes a bZIP transcription factor that binds to the cAMP responsive element found in many viral and cellular promoters. It is an important component of cAMP-mediated signal transduction during the spermatogenetic cycle, as well as other complex processes. Alternative promoter and translation initiation site usage allows this gene to exert spatial and temporal specificity to cAMP responsiveness. Multiple alternatively spliced transcript variants encoding several different isoforms have been found for this gene, with some of them functioning as activators and some as repressors of transcription.[7]

Gene location

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The chromosomal location of CREM gene is at 10p11.21, where it starts at 35415769 and ends at 35501886 bp from pter ( according to hg19-Feb_2009)[13]

Interactions

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CAMP responsive element modulator has been shown to interact with FHL5.[14][15]

Disease relevance of CREM

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Panic disorder

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One study reported the DNA sequence variations in the gene for CREM in panic disorder patients. It showed a significant excess of the shorter eight-repeat allele and of genotypes containing the eight-repeat allele in panic disorder patients.[16] The observed associations were limited to panic disorder without agoraphobia, and they were more prominent in females. But, the independent Italian and Spanish samples in this study did not support their results. Another family-based study showed little evidence of any susceptibility locus for panic disorder either within the CREM gene or in a nearby region on chromosome 10p11[17]

Spermiogenesis deficiency

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CREM has been shown to be a master-switch regulator in testis.[18] It plays an important role in the regulation of the expression of post-meiotic genes, and this has been supported by several studies using CREM-mutation mice.[19] The results showed the first step in the process of sperm formation would be blocked if the germ cell development in mice CREM gene were disrupted. The cAMP response element sites can be found in the promoter region of some postmeiotic genes, so that the CREM can target and regulate these genes.[18]

Two studies proved that treat the rats with Salvia hypoleuca and Alpina galanga can significantly increased the CREM gene expression.[20][21]

Systemic lupus erythematousus

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Less IL-2 will be produced from T cells in humans or mice with systemic lupus erythematousus (SLE). Some studies showed that an increased level CREM was presented in the nucleus of T lymphocytes from SLE patients. The CREM bound to the -180 site of the IL-2 promoter to repress its transcription.[22]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000095794 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000063889 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Meyer TE, Habener JF (November 1992). "Cyclic AMP response element binding protein CREB and modulator protein CREM are products of distinct genes". Nucleic Acids Research. 20 (22): 6106. doi:10.1093/nar/20.22.6106. PMC 334485. PMID 1461747.
  6. ^ Masquilier D, Foulkes NS, Mattei MG, Sassone-Corsi P (November 1993). "Human CREM gene: evolutionary conservation, chromosomal localization, and inducibility of the transcript". Cell Growth & Differentiation. 4 (11): 931–937. PMID 7916662.
  7. ^ a b "Entrez Gene: CREM cAMP responsive element modulator".
  8. ^ Foulkes NS, Sassone-Corsi P (February 1992). "More is better: activators and repressors from the same gene". Cell. 68 (3): 411–414. doi:10.1016/0092-8674(92)90178-f. PMID 1739963. S2CID 34290449.
  9. ^ Sassone-Corsi P (1995-01-01). "Transcription factors responsive to cAMP". Annual Review of Cell and Developmental Biology. 11: 355–377. doi:10.1146/annurev.cb.11.110195.002035. PMID 8689562.
  10. ^ Isoda T, Paolocci N, Haghighi K, Wang C, Wang Y, Georgakopoulos D, et al. (February 2003). "Novel regulation of cardiac force-frequency relation by CREM (cAMP response element modulator)". FASEB Journal. 17 (2): 144–151. doi:10.1096/fj.01-0981com. PMID 12554693. S2CID 17890025.
  11. ^ Sassone-Corsi P (June 2000). "CREM: a master-switch regulating the balance between differentiation and apoptosis in male germ cells". Molecular Reproduction and Development. 56 (2 Suppl): 228–229. doi:10.1002/(SICI)1098-2795(200006)56:2+<228::AID-MRD2>3.0.CO;2-B. PMID 10824972. S2CID 21160055.
  12. ^ Sassone-Corsi P (August 1998). "CREM: a master-switch governing male germ cells differentiation and apoptosis". Seminars in Cell & Developmental Biology. 9 (4): 475–482. doi:10.1006/scdb.1998.0200. PMID 9813195.
  13. ^ "CREM (cAMP responsive element modulator)". atlasgeneticsoncology.org. Retrieved 2016-10-16.
  14. ^ Fimia GM, De Cesare D, Sassone-Corsi P (November 2000). "A family of LIM-only transcriptional coactivators: tissue-specific expression and selective activation of CREB and CREM". Molecular and Cellular Biology. 20 (22): 8613–8622. doi:10.1128/MCB.20.22.8613-8622.2000. PMC 102166. PMID 11046156.
  15. ^ Fimia GM, De Cesare D, Sassone-Corsi P (March 1999). "CBP-independent activation of CREM and CREB by the LIM-only protein ACT". Nature. 398 (6723): 165–169. Bibcode:1999Natur.398..165F. doi:10.1038/18237. PMID 10086359. S2CID 4424908.
  16. ^ Domschke K, Kuhlenbäumer G, Schirmacher A, Lorenzi C, Armengol L, DiBella D, et al. (February 2003). "Human nuclear transcription factor gene CREM: genomic organization, mutation screening, and association analysis in panic disorder". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 117B (1): 70–78. doi:10.1002/ajmg.b.10018. PMID 12555239. S2CID 8884044.
  17. ^ Hamilton SP, Slager SL, Mayo D, Heiman GA, Klein DF, Hodge SE, et al. (April 2004). "Investigation of polymorphisms in the CREM gene in panic disorder". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 126B (1): 111–115. doi:10.1002/ajmg.b.20121. PMID 15048659. S2CID 43810849.
  18. ^ a b Krausz C, Sassone-Corsi P (January 2005). "Genetic control of spermiogenesis: insights from the CREM gene and implications for human infertility". Reproductive Biomedicine Online. 10 (1): 64–71. doi:10.1016/S1472-6483(10)60805-X. PMID 15705296.
  19. ^ Nantel F, Monaco L, Foulkes NS, Masquilier D, LeMeur M, Henriksén K, et al. (March 1996). "Spermiogenesis deficiency and germ-cell apoptosis in CREM-mutant mice". Nature. 380 (6570): 159–162. Bibcode:1996Natur.380..159N. doi:10.1038/380159a0. PMID 8600390. S2CID 4278745.
  20. ^ Jasem E, Nasim J, Gholamreza M, Naser S, Nader M, Maryam SL, et al. (October 2010). "Evaluation of the effects of Salvia hypoleuca on the cAMP-responsive element modulator (CREM) gene expression and spermatogenesis in rat". Middle East Fertility Society Journal. 15 (4): 274–277. doi:10.1016/j.mefs.2010.08.002.
  21. ^ Mazaheri M, Shahdadi V, Nazari Boron A (November 2014). "Molecullar and biochemical effect of alcohlic extract of Alpinia galanga on rat spermatogenesis process". Iranian Journal of Reproductive Medicine. 12 (11): 765–770. PMC 4330656. PMID 25709632.
  22. ^ Juang YT, Wang Y, Solomou EE, Li Y, Mawrin C, Tenbrock K, et al. (April 2005). "Systemic lupus erythematosus serum IgG increases CREM binding to the IL-2 promoter and suppresses IL-2 production through CaMKIV". The Journal of Clinical Investigation. 115 (4): 996–1005. doi:10.1172/JCI22854. PMC 1070410. PMID 15841182.

Further reading

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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