CAMP responsive element modulator

Last updated
CREM
Protein CREM PDB 1dh3.png
Identifiers
Aliases CREM , CREM-2, ICER, hCREM-2, cAMP responsive element modulator
External IDs OMIM: 123812 MGI: 88495 HomoloGene: 84591 GeneCards: CREM
Orthologs
SpeciesHumanMouse
Entrez

1390

12916

Ensembl

ENSG00000095794

ENSMUSG00000063889

UniProt

Q03060

P27699

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

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]

Function

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

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

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

Disease relevance of CREM

Panic disorder

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

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

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]

Related Research Articles

<span class="mw-page-title-main">CREB</span> Class of proteins

CREB-TF is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes. CREB was first described in 1987 as a cAMP-responsive transcription factor regulating the somatostatin gene.

<span class="mw-page-title-main">Transcription factor Sp1</span> Protein-coding gene in the species Homo sapiens

Transcription factor Sp1, also known as specificity protein 1* is a protein that in humans is encoded by the SP1 gene.

<span class="mw-page-title-main">Protein c-Fos</span> Mammalian protein found in Homo sapiens

Protein c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It is encoded in humans by the FOS gene. It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV. It is a part of a bigger Fos family of transcription factors which includes c-Fos, FosB, Fra-1 and Fra-2. It has been mapped to chromosome region 14q21→q31. c-Fos encodes a 62 kDa protein, which forms heterodimer with c-jun, resulting in the formation of AP-1 complex which binds DNA at AP-1 specific sites at the promoter and enhancer regions of target genes and converts extracellular signals into changes of gene expression. It plays an important role in many cellular functions and has been found to be overexpressed in a variety of cancers.

<span class="mw-page-title-main">CEBPB</span> Protein-coding gene in the species Homo sapiens

CCAAT/enhancer-binding protein beta is a protein that in humans is encoded by the CEBPB gene.

<span class="mw-page-title-main">CREB1</span> Mammalian protein found in Homo sapiens

CAMP responsive element binding protein 1, also known as CREB-1, is a protein that in humans is encoded by the CREB1 gene. This protein binds the cAMP response element, a DNA nucleotide sequence present in many viral and cellular promoters. The binding of CREB1 stimulates transcription.

<span class="mw-page-title-main">ATF3</span> Protein-coding gene in the species Homo sapiens

Cyclic AMP-dependent transcription factor ATF-3 is a protein that, in humans, is encoded by the ATF3 gene.

<span class="mw-page-title-main">ATF1</span> Protein-coding gene in humans

Cyclic AMP-dependent transcription factor ATF-1 is a protein that in humans is encoded by the ATF1 gene.

<span class="mw-page-title-main">ATF4</span> Mammalian protein found in Homo sapiens

Activating transcription factor 4 , also known as ATF4, is a protein that in humans is encoded by the ATF4 gene.

<span class="mw-page-title-main">CAMK2G</span> Protein-coding gene in the species Homo sapiens

Calcium/calmodulin-dependent protein kinase type II gamma chain is an enzyme that in humans is encoded by the CAMK2G gene.

<span class="mw-page-title-main">Activating transcription factor 2</span> Protein-coding gene in the species Homo sapiens

Activating transcription factor 2, also known as ATF2, is a protein that, in humans, is encoded by the ATF2 gene.

<span class="mw-page-title-main">RPS6KA3</span> Enzyme found in humans

protein S6 kinase, 90kDa, polypeptide 3, also s RPS6KA3, is an enzyme that in humans is encoded by the RPS6KA3 gene.

<span class="mw-page-title-main">RPS6KA2</span> Enzyme found in humans

Ribosomal protein S6 kinase alpha-2 is an enzyme that in humans is encoded by the RPS6KA2 gene.

<span class="mw-page-title-main">CREB3</span> Protein-coding gene in the species Homo sapiens

Cyclic AMP-responsive element-binding protein 3 is a protein that in humans is encoded by the CREB3 gene.

<span class="mw-page-title-main">FHL5</span> Protein-coding gene in the species Homo sapiens

Four and a half LIM domains protein 5 is a protein that in humans is encoded by the FHL5 gene.

<span class="mw-page-title-main">ATF5</span> Protein-coding gene in the species Homo sapiens

Activating transcription factor 5, also known as ATF5, is a protein that, in humans, is encoded by the ATF5 gene.

<span class="mw-page-title-main">CREBL1</span> Protein-coding gene in the species Homo sapiens

CAMP responsive element binding protein-like 1, also known as CREBL1, is a protein which in humans is encoded by the CREBL1 gene.

<span class="mw-page-title-main">RFX2</span> Protein-coding gene in the species Homo sapiens

DNA-binding protein RFX2 is a protein that in humans is encoded by the RFX2 gene.

The gal operon is a prokaryotic operon, which encodes enzymes necessary for galactose metabolism. Repression of gene expression for this operon works via binding of repressor molecules to two operators. These repressors dimerize, creating a loop in the DNA. The loop as well as hindrance from the external operator prevent RNA polymerase from binding to the promoter, and thus prevent transcription. Additionally, since the metabolism of galactose in the cell is involved in both anabolic and catabolic pathways, a novel regulatory system using two promoters for differential repression has been identified and characterized within the context of the gal operon.

bZIP domain Protein domain

The Basic Leucine Zipper Domain is found in many DNA binding eukaryotic proteins. One part of the domain contains a region that mediates sequence specific DNA binding properties and the leucine zipper that is required to hold together (dimerize) two DNA binding regions. The DNA binding region comprises a number of basic amino acids such as arginine and lysine. Proteins containing this domain are transcription factors.

Paolo Sassone-Corsi was an Italian molecular biologist, epigeneticist, and researcher. He is known for his contributions in the areas of transcriptional regulation, epigenetics, circadian biology, and metabolic regulation. He is known for his contributions in the areas of transcriptional regulation, epigenetics, circadian biology, and metabolic regulation. His research primarily focused on the mechanisms that regulate transcription and their relation to metabolism and circadian clocks. His work focused on understanding how the circadian clock regulates metabolic cycles. Most notably, he discovered that SIRT1, a histone deacetylase with a critical role in gene expression and metabolism, is able to regulate the activity of the CLOCK protein. In 2011, Sassone-Corsi founded and directed the “Center for Epigenetics and Metabolism” at the University of California, Irvine.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000095794 - Ensembl, May 2017
  2. 1 2 3 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 (Nov 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 (Nov 1993). "Human CREM gene: evolutionary conservation, chromosomal localization, and inducibility of the transcript". Cell Growth & Differentiation. 4 (11): 931–7. PMID   7916662.
  7. 1 2 "Entrez Gene: CREM cAMP responsive element modulator".
  8. ↑ Foulkes, N. S.; Sassone-Corsi, P. (1992-02-07). "More is better: activators and repressors from the same gene". Cell. 68 (3): 411–414. doi:10.1016/0092-8674(92)90178-f. ISSN   0092-8674. 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. ISSN   1081-0706. PMID   8689562.
  10. ↑ Isoda, Takayoshi; Paolocci, Nazareno; Haghighi, Kobra; Wang, Congrong; Wang, Yibin; Georgakopoulos, Dimitrios; Servillo, Giuseppe; Della Fazia, Maria Agnese; Kranias, Evangelia G. (2003-02-01). "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. ISSN   1530-6860. PMID   12554693. S2CID   17890025.
  11. ↑ Sassone-Corsi, P. (2000-06-01). "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 . ISSN   1040-452X. PMID   10824972. S2CID   21160055.
  12. ↑ Sassone-Corsi, P. (1998-08-01). "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. ISSN   1084-9521. PMID   9813195.
  13. ↑ "CREM (cAMP responsive element modulator)". atlasgeneticsoncology.org. Retrieved 2016-10-16.
  14. ↑ Fimia GM, De Cesare D, Sassone-Corsi P (Nov 2000). "A family of LIM-only transcriptional coactivators: tissue-specific expression and selective activation of CREB and CREM". Molecular and Cellular Biology. 20 (22): 8613–22. doi:10.1128/MCB.20.22.8613-8622.2000. PMC   102166 . PMID   11046156.
  15. ↑ Fimia GM, De Cesare D, Sassone-Corsi P (Mar 1999). "CBP-independent activation of CREM and CREB by the LIM-only protein ACT". Nature. 398 (6723): 165–9. 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.; Gratacos, M.; Garritsen, H. S.; Nöthen, M. M. (2003-02-01). "Human nuclear transcription factor gene CREM: genomic organization, mutation screening, and association analysis in panic disorder". American Journal of Medical Genetics Part B. 117B (1): 70–78. doi:10.1002/ajmg.b.10018. ISSN   1552-4841. PMID   12555239. S2CID   8884044.
  17. ↑ Hamilton, Steven P.; Slager, Susan L.; Mayo, David; Heiman, Gary A.; Klein, Donald F.; Hodge, Susan E.; Fyer, Abby J.; Weissman, Myrna M.; Knowles, James A. (2004-04-01). "Investigation of polymorphisms in the CREM gene in panic disorder". American Journal of Medical Genetics Part B. 126B (1): 111–115. doi:10.1002/ajmg.b.20121. ISSN   1552-4841. PMID   15048659. S2CID   43810849.
  18. 1 2 Krausz, Csilla; Sassone-Corsi, Paolo (2005-01-01). "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, N. S.; Masquilier, D.; LeMeur, M.; Henriksén, K.; Dierich, A.; Parvinen, M.; Sassone-Corsi, P. (1996-03-14). "Spermiogenesis deficiency and germ-cell apoptosis in CREM-mutant mice". Nature. 380 (6570): 159–162. Bibcode:1996Natur.380..159N. doi:10.1038/380159a0. ISSN   0028-0836. PMID   8600390. S2CID   4278745.
  20. ↑ Jasem, Estakhr; Nasim, Javdan; Gholamreza, Motalleb; Naser, Sanchooli; Nader, Marzban; Maryam, Shams Lahijani; Abbas, Nikravesh; Vahid, Rostamian (2010-10-01). "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, Mahta; Shahdadi, Vahid; Nazari Boron, Ashraf (2016-10-16). "Molecullar and biochemical effect of alcoholic extract of Alpinia galanga on rat spermatogenesis process". Iranian Journal of Reproductive Medicine. 12 (11): 765–770. ISSN   1680-6433. PMC   4330656 . PMID   25709632.
  22. ↑ Juang, Yuang-Taung; Wang, Ying; Solomou, Elena E.; Li, Yansong; Mawrin, Christian; Tenbrock, Klaus; Kyttaris, Vasileios C.; Tsokos, George C. (2005-04-01). "Systemic lupus erythematosus serum IgG increases CREM binding to the IL-2 promoter and suppresses IL-2 production through CaMKIV". Journal of Clinical Investigation. 115 (4): 996–1005. doi:10.1172/JCI22854. ISSN   0021-9738. PMC   1070410 . PMID   15841182.

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