CAMP responsive element modulator: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
{{DISPLAYTITLE:cAMP responsive element modulator}}
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'''cAMP responsive element modulator''' is a [[protein]] that in humans is encoded by the '''CREM''' [[gene]],<ref name="pmid1461747">{{cite journal | vauthors = Meyer TE, Habener JF | title = Cyclic AMP response element binding protein CREB and modulator protein CREM are products of distinct genes | journal = Nucleic Acids Research | volume = 20 | issue = 22 | pages = 6106 | date = Nov 1992 | pmid = 1461747 | pmc = 334485 | doi = 10.1093/nar/20.22.6106 }}</ref><ref name="pmid7916662">{{cite journal | vauthors = Masquilier D, Foulkes NS, Mattei MG, Sassone-Corsi P | title = Human CREM gene: evolutionary conservation, chromosomal localization, and inducibility of the transcript | journal = Cell Growth & Differentiation | volume = 4 | issue = 11 | pages = 931–7 | date = Nov 1993 | pmid = 7916662 | pmc =  | doi =  }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: CREM cAMP responsive element modulator| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1390| accessdate = }}</ref> and it belongs to the cAMP-responsive element binding protein family. It has multiple isoforms, which act either as repressors or activators.<ref>{{Cite journal|last=Foulkes|first=N. S.|last2=Sassone-Corsi|first2=P.|date=1992-02-07|title=More is better: activators and repressors from the same gene|pmid=1739963|journal=Cell|volume=68|issue=3|pages=411–414|issn=0092-8674|doi=10.1016/0092-8674(92)90178-f}}</ref> CREB family is important for in regulating transcription in response to various stresses, metabolic and developmental signals.<ref>{{Cite journal|last=Sassone-Corsi|first=P.|date=1995-01-01|title=Transcription factors responsive to cAMP|pmid=8689562|journal=Annual Review of Cell and Developmental Biology|volume=11|pages=355–377|doi=10.1146/annurev.cb.11.110195.002035|issn=1081-0706}}</ref> CREM transcription factors also play an important role in many physiological systems, such as cardiac function,<ref>{{Cite journal|last=Isoda|first=Takayoshi|last2=Paolocci|first2=Nazareno|last3=Haghighi|first3=Kobra|last4=Wang|first4=Congrong|last5=Wang|first5=Yibin|last6=Georgakopoulos|first6=Dimitrios|last7=Servillo|first7=Giuseppe|last8=Della Fazia|first8=Maria Agnese|last9=Kranias|first9=Evangelia G.|date=2003-02-01|title=Novel regulation of cardiac force-frequency relation by CREM (cAMP response element modulator)|pmid=12554693|journal=FASEB journal: official publication of the Federation of American Societies for Experimental Biology|volume=17|issue=2|pages=144–151|doi=10.1096/fj.01-0981com|issn=1530-6860}}</ref> circadian rhythms,<ref>{{Cite journal|last=Sassone-Corsi|first=P.|date=2000-06-01|title=CREM: a master-switch regulating the balance between differentiation and apoptosis in male germ cells|pmid=10824972|journal=Molecular Reproduction and Development|volume=56|issue=2 Suppl|pages=228–229|doi=10.1002/(SICI)1098-2795(200006)56:2+<228::AID-MRD2>3.0.CO;2-B|issn=1040-452X}}</ref> locomotion and spermatogenesis.<ref>{{Cite journal|last=Sassone-Corsi|first=P.|date=1998-08-01|title=CREM: a master-switch governing male germ cells differentiation and apoptosis|pmid=9813195|journal=Seminars in Cell & Developmental Biology|volume=9|issue=4|pages=475–482|doi=10.1006/scdb.1998.0200|issn=1084-9521}}</ref>
| require_manual_inspection = no
| update_protein_box = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image = PBB_Protein_CREM_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1dh3.
| PDB = {{PDB2|1dh3}}
| Name = CAMP responsive element modulator
| HGNCid = 2352
| Symbol = CREM
| AltSymbols =; ICER; MGC111110; MGC17881; MGC41893; hCREM-2
| OMIM = 123812
| ECnumber = 
| Homologene = 84591
| MGIid = 
| GeneAtlas_image1 = PBB_GE_CREM_207630_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_CREM_209967_s_at_tn.png
| GeneAtlas_image3 = PBB_GE_CREM_210171_s_at_tn.png
| Function = {{GNF_GO|id=GO:0003700 |text = transcription factor activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0008140 |text = cAMP response element binding protein binding}} {{GNF_GO|id=GO:0043565 |text = sequence-specific DNA binding}} {{GNF_GO|id=GO:0046983 |text = protein dimerization activity}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0006350 |text = transcription}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0007165 |text = signal transduction}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 1390
    | Hs_Ensembl = ENSG00000095794
    | Hs_RefseqProtein = NP_001872
    | Hs_RefseqmRNA = NM_001881
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 10
    | Hs_GenLoc_start = 35455807
    | Hs_GenLoc_end = 35541892
    | Hs_Uniprot = Q03060
    | Mm_EntrezGene = 
    | Mm_Ensembl = 
    | Mm_RefseqmRNA = 
    | Mm_RefseqProtein = 
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 
    | Mm_GenLoc_start = 
    | Mm_GenLoc_end = 
    | Mm_Uniprot = 
  }}
}}
'''CAMP responsive element modulator''', also known as '''CREM''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: CREM cAMP responsive element modulator| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1390| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
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 transcriptnhunion.<ref name="entrez" />
{{PBB_Summary
| section_title =
| summary_text = 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.<ref name="entrez">{{cite web | title = Entrez Gene: CREM cAMP responsive element modulator| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1390| accessdate = }}</ref>
}}


==References==
== Gene location ==
{{reflist|2}}
The chromosomal location of CREM gene is 10p11.21, and it starts at 35415769 and ends at 35501886 bp from pter ( according to hg19-Feb_2009)<ref>{{Cite web|url=http://atlasgeneticsoncology.org/Genes/GC_CREM.html|title=CREM (cAMP responsive element modulator)|website=atlasgeneticsoncology.org|access-date=2016-10-16}}</ref>
==Further reading==
 
== Interactions ==
 
CAMP responsive element modulator has been shown to [[Protein-protein interaction|interact]] with [[FHL5]].<ref name=pmid11046156>{{cite journal | vauthors = Fimia GM, De Cesare D, Sassone-Corsi P | title = A family of LIM-only transcriptional coactivators: tissue-specific expression and selective activation of CREB and CREM | journal = Molecular and Cellular Biology | volume = 20 | issue = 22 | pages = 8613–22 | date = Nov 2000 | pmid = 11046156 | pmc = 102166 | doi = 10.1128/MCB.20.22.8613-8622.2000 }}</ref><ref name=pmid10086359>{{cite journal | vauthors = Fimia GM, De Cesare D, Sassone-Corsi P | title = CBP-independent activation of CREM and CREB by the LIM-only protein ACT | journal = Nature | volume = 398 | issue = 6723 | pages = 165–9 | date = Mar 1999 | pmid = 10086359 | doi = 10.1038/18237 }}</ref>
 
== 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.<ref>{{Cite journal|last=Domschke|first=K.|last2=Kuhlenbäumer|first2=G.|last3=Schirmacher|first3=A.|last4=Lorenzi|first4=C.|last5=Armengol|first5=L.|last6=DiBella|first6=D.|last7=Gratacos|first7=M.|last8=Garritsen|first8=H. S.|last9=Nöthen|first9=M. M.|date=2003-02-01|title=Human nuclear transcription factor gene CREM: genomic organization, mutation screening, and association analysis in panic disorder|pmid=12555239|journal=American Journal of Medical Genetics Part B|volume=117B|issue=1|pages=70–78|doi=10.1002/ajmg.b.10018|issn=1552-4841}}</ref> 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<ref>{{Cite journal|last=Hamilton|first=Steven P.|last2=Slager|first2=Susan L.|last3=Mayo|first3=David|last4=Heiman|first4=Gary A.|last5=Klein|first5=Donald F.|last6=Hodge|first6=Susan E.|last7=Fyer|first7=Abby J.|last8=Weissman|first8=Myrna M.|last9=Knowles|first9=James A.|date=2004-04-01|title=Investigation of polymorphisms in the CREM gene in panic disorder|pmid=15048659|journal=American Journal of Medical Genetics Part B|volume=126B|issue=1|pages=111–115|doi=10.1002/ajmg.b.20121|issn=1552-4841}}</ref>
 
=== Spermiogenesis deficiency ===
Like [[:fr:Paolo Sassone-Corsi|Dr. Paolo Sassone-Corsi]] wrote in this article CREM is “a master-switch regulator in testis”.<ref name="Krausz 64–71">{{Cite journal|last=Krausz|first=Csilla|last2=Sassone-Corsi|first2=Paolo|date=2005-01-01|title=Genetic control of spermiogenesis: insights from the CREM gene and implications for human infertility|url=http://www.sciencedirect.com/science/article/pii/S147264831060805X|journal=Reproductive BioMedicine Online|volume=10|issue=1|pages=64–71|doi=10.1016/S1472-6483(10)60805-X}}</ref> 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.<ref>{{Cite journal|last=Nantel|first=F.|last2=Monaco|first2=L.|last3=Foulkes|first3=N. S.|last4=Masquilier|first4=D.|last5=LeMeur|first5=M.|last6=Henriksén|first6=K.|last7=Dierich|first7=A.|last8=Parvinen|first8=M.|last9=Sassone-Corsi|first9=P.|date=1996-03-14|title=Spermiogenesis deficiency and germ-cell apoptosis in CREM-mutant mice|pmid=8600390|journal=Nature|volume=380|issue=6570|pages=159–162|doi=10.1038/380159a0|issn=0028-0836}}</ref> 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.<ref name="Krausz 64–71"/>
 
Two studies proved that treat the rats with ''Salvia hypoleuca'' and ''Alpina galanga'' can significantly increased the CREM gene expression.<ref>{{Cite journal|last=Jasem|first=Estakhr|last2=Nasim|first2=Javdan|last3=Gholamreza|first3=Motalleb|last4=Naser|first4=Sanchooli|last5=Nader|first5=Marzban|last6=Maryam|first6=Shams Lahijani|last7=Abbas|first7=Nikravesh|last8=Vahid|first8=Rostamian|date=2010-10-01|title=Evaluation of the effects of Salvia hypoleuca on the cAMP-responsive element modulator (CREM) gene expression and spermatogenesis in rat|url=http://www.sciencedirect.com/science/article/pii/S1110569010000981|journal=Middle East Fertility Society Journal|volume=15|issue=4|pages=274–277|doi=10.1016/j.mefs.2010.08.002}}</ref><ref>{{Cite journal|last=Mazaheri|first=Mahta|last2=Shahdadi|first2=Vahid|last3=Nazari Boron|first3=Ashraf|date=2016-10-16|title=Molecullar and biochemical effect of alcohlic extract of Alpinia galanga on rat spermatogenesis process|pmc=4330656|journal=Iranian Journal of Reproductive Medicine|volume=12|issue=11|pages=765–770|issn=1680-6433|pmid=25709632}}</ref>
 
=== Systemic lupus erythematousus ===
Less [[IL-2 receptor|IL-2]] will be produced from [[T cell]]s in humans or mice with [[Lupus erythematosus|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.<ref>{{Cite journal|last=Juang|first=Yuang-Taung|last2=Wang|first2=Ying|last3=Solomou|first3=Elena E.|last4=Li|first4=Yansong|last5=Mawrin|first5=Christian|last6=Tenbrock|first6=Klaus|last7=Kyttaris|first7=Vasileios C.|last8=Tsokos|first8=George C.|date=2005-04-01|title=Systemic lupus erythematosus serum IgG increases CREM binding to the IL-2 promoter and suppresses IL-2 production through CaMKIV|pmc=1070410|journal=Journal of Clinical Investigation|volume=115|issue=4|pages=996–1005|doi=10.1172/JCI22854|issn=0021-9738|pmid=15841182}}</ref>
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Don J, Stelzer G | title = The expanding family of CREB/CREM transcription factors that are involved with spermatogenesis | journal = Molecular and Cellular Endocrinology | volume = 187 | issue = 1-2 | pages = 115–24 | date = Feb 2002 | pmid = 11988318 | doi = 10.1016/S0303-7207(01)00696-7 }}
| citations =
* {{cite journal | vauthors = Yan C, Miller CL, Abe J | title = Regulation of phosphodiesterase 3 and inducible cAMP early repressor in the heart | journal = Circulation Research | volume = 100 | issue = 4 | pages = 489–501 | date = Mar 2007 | pmid = 17332439 | doi = 10.1161/01.RES.0000258451.44949.d7 | pmc = 4115784 }}
*{{cite journal | author=Don J, Stelzer G |title=The expanding family of CREB/CREM transcription factors that are involved with spermatogenesis. |journal=Mol. Cell. Endocrinol. |volume=187 |issue= 1-2 |pages= 115-24 |year= 2003 |pmid= 11988318 |doi= }}
* {{cite journal | vauthors = Pongubala JM, Atchison ML | title = Activating transcription factor 1 and cyclic AMP response element modulator can modulate the activity of the immunoglobulin kappa 3' enhancer | journal = The Journal of Biological Chemistry | volume = 270 | issue = 17 | pages = 10304–13 | date = Apr 1995 | pmid = 7730336 | doi = 10.1074/jbc.270.17.10304 }}
*{{cite journal | author=Yan C, Miller CL, Abe J |title=Regulation of phosphodiesterase 3 and inducible cAMP early repressor in the heart. |journal=Circ. Res. |volume=100 |issue= 4 |pages= 489-501 |year= 2007 |pmid= 17332439 |doi= 10.1161/01.RES.0000258451.44949.d7 }}
* {{cite journal | vauthors = Walker WH, Sanborn BM, Habener JF | title = An isoform of transcription factor CREM expressed during spermatogenesis lacks the phosphorylation domain and represses cAMP-induced transcription | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 91 | issue = 26 | pages = 12423–7 | date = Dec 1994 | pmid = 7809053 | pmc = 45450 | doi = 10.1073/pnas.91.26.12423 }}
*{{cite journal  | author=Meyer TE, Habener JF |title=Cyclic AMP response element binding protein CREB and modulator protein CREM are products of distinct genes. |journal=Nucleic Acids Res. |volume=20 |issue= 22 |pages= 6106 |year= 1993 |pmid= 1461747 |doi=  }}
* {{cite journal | vauthors = Fujimoto T, Fujisawa J, Yoshida M | title = Novel isoforms of human cyclic AMP-responsive element modulator (hCREM) mRNA | journal = Journal of Biochemistry | volume = 115 | issue = 2 | pages = 298–303 | date = Feb 1994 | pmid = 8206879 | doi =  }}
*{{cite journal | author=Pongubala JM, Atchison ML |title=Activating transcription factor 1 and cyclic AMP response element modulator can modulate the activity of the immunoglobulin kappa 3' enhancer. |journal=J. Biol. Chem. |volume=270 |issue= 17 |pages= 10304-13 |year= 1995 |pmid= 7730336 |doi= }}
* {{cite journal | vauthors = de Groot RP, den Hertog J, Vandenheede JR, Goris J, Sassone-Corsi P | title = Multiple and cooperative phosphorylation events regulate the CREM activator function | journal = The EMBO Journal | volume = 12 | issue = 10 | pages = 3903–11 | date = Oct 1993 | pmid = 8404858 | pmc = 413673 | doi =  }}
*{{cite journal | author=Walker WH, Sanborn BM, Habener JF |title=An isoform of transcription factor CREM expressed during spermatogenesis lacks the phosphorylation domain and represses cAMP-induced transcription. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=91 |issue= 26 |pages= 12423-7 |year= 1995 |pmid= 7809053 |doi= }}
* {{cite journal | vauthors = Bodor J, Walker W, Flemington E, Spetz AL, Habener JF | title = Modulation of Tax and PKA-mediated expression of HTLV-I promoter via cAMP response element binding and modulator proteins CREB and CREM | journal = FEBS Letters | volume = 377 | issue = 3 | pages = 413–8 | date = Dec 1995 | pmid = 8549766 | doi = 10.1016/0014-5793(95)01299-0 }}
*{{cite journal  | author=Masquilier D, Foulkes NS, Mattei MG, Sassone-Corsi P |title=Human CREM gene: evolutionary conservation, chromosomal localization, and inducibility of the transcript. |journal=Cell Growth Differ. |volume=4 |issue= 11 |pages= 931-7 |year= 1994 |pmid= 7916662 |doi=  }}
* {{cite journal | vauthors = Nantel F, Monaco L, Foulkes NS, Masquilier D, LeMeur M, Henriksén K, Dierich A, Parvinen M, Sassone-Corsi P | title = Spermiogenesis deficiency and germ-cell apoptosis in CREM-mutant mice | journal = Nature | volume = 380 | issue = 6570 | pages = 159–62 | date = Mar 1996 | pmid = 8600390 | doi = 10.1038/380159a0 }}
*{{cite journal | author=Fujimoto T, Fujisawa J, Yoshida M |title=Novel isoforms of human cyclic AMP-responsive element modulator (hCREM) mRNA. |journal=J. Biochem. |volume=115 |issue= 2 |pages= 298-303 |year= 1994 |pmid= 8206879 |doi=  }}
* {{cite journal | vauthors = Blendy JA, Kaestner KH, Weinbauer GF, Nieschlag E, Schütz G | title = Severe impairment of spermatogenesis in mice lacking the CREM gene | journal = Nature | volume = 380 | issue = 6570 | pages = 162–5 | date = Mar 1996 | pmid = 8600391 | doi = 10.1038/380162a0 }}
*{{cite journal | author=de Groot RP, den Hertog J, Vandenheede JR, ''et al.'' |title=Multiple and cooperative phosphorylation events regulate the CREM activator function. |journal=EMBO J. |volume=12 |issue= 10 |pages= 3903-11 |year= 1993 |pmid= 8404858 |doi=  }}
* {{cite journal | vauthors = Bodor J, Spetz AL, Strominger JL, Habener JF | title = cAMP inducibility of transcriptional repressor ICER in developing and mature human T lymphocytes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 8 | pages = 3536–41 | date = Apr 1996 | pmid = 8622971 | pmc = 39645 | doi = 10.1073/pnas.93.8.3536 }}
*{{cite journal | author=Bodor J, Walker W, Flemington E, ''et al.'' |title=Modulation of Tax and PKA-mediated expression of HTLV-I promoter via cAMP response element binding and modulator proteins CREB and CREM. |journal=FEBS Lett. |volume=377 |issue= 3 |pages= 413-8 |year= 1996 |pmid= 8549766 |doi= 10.1016/0014-5793(95)01299-0 }}
* {{cite journal | vauthors = Gellersen B, Kempf R, Telgmann R | title = Human endometrial stromal cells express novel isoforms of the transcriptional modulator CREM and up-regulate ICER in the course of decidualization | journal = Molecular Endocrinology | volume = 11 | issue = 1 | pages = 97–113 | date = Jan 1997 | pmid = 8994192 | doi = 10.1210/me.11.1.97 }}
*{{cite journal | author=Nantel F, Monaco L, Foulkes NS, ''et al.'' |title=Spermiogenesis deficiency and germ-cell apoptosis in CREM-mutant mice. |journal=Nature |volume=380 |issue= 6570 |pages= 159-62 |year= 1996 |pmid= 8600390 |doi= 10.1038/380159a0 }}
* {{cite journal | vauthors = Laurance ME, Kwok RP, Huang MS, Richards JP, Lundblad JR, Goodman RH | title = Differential activation of viral and cellular promoters by human T-cell lymphotropic virus-1 tax and cAMP-responsive element modulator isoforms | journal = The Journal of Biological Chemistry | volume = 272 | issue = 5 | pages = 2646–51 | date = Jan 1997 | pmid = 9006899 | doi = 10.1074/jbc.272.5.2646 }}
*{{cite journal | author=Blendy JA, Kaestner KH, Weinbauer GF, ''et al.'' |title=Severe impairment of spermatogenesis in mice lacking the CREM gene. |journal=Nature |volume=380 |issue= 6570 |pages= 162-5 |year= 1996 |pmid= 8600391 |doi= 10.1038/380162a0 }}
* {{cite journal | vauthors = Bonny C, Cooker LA, Goldberg E | title = Deoxyribonucleic acid-protein interactions and expression of the human testis-specific lactate dehydrogenase promoter: transcription factor Sp1 plays a major role | journal = Biology of Reproduction | volume = 58 | issue = 3 | pages = 754–9 | date = Mar 1998 | pmid = 9510963 | doi = 10.1095/biolreprod58.3.754 }}
*{{cite journal | author=Bodor J, Spetz AL, Strominger JL, Habener JF |title=cAMP inducibility of transcriptional repressor ICER in developing and mature human T lymphocytes. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=93 |issue= 8 |pages= 3536-41 |year= 1996 |pmid= 8622971 |doi= }}
* {{cite journal | vauthors = Müller FU, Bokník P, Knapp J, Neumann J, Vahlensieck U, Oetjen E, Scheld HH, Schmitz W | title = Identification and expression of a novel isoform of cAMP response element modulator in the human heart | journal = FASEB Journal | volume = 12 | issue = 12 | pages = 1191–9 | date = Sep 1998 | pmid = 9737722 | doi =  }}
*{{cite journal | author=Gellersen B, Kempf R, Telgmann R |title=Human endometrial stromal cells express novel isoforms of the transcriptional modulator CREM and up-regulate ICER in the course of decidualization. |journal=Mol. Endocrinol. |volume=11 |issue= 1 |pages= 97-113 |year= 1997 |pmid= 8994192 |doi= }}
* {{cite journal | vauthors = Fimia GM, De Cesare D, Sassone-Corsi P | title = CBP-independent activation of CREM and CREB by the LIM-only protein ACT | journal = Nature | volume = 398 | issue = 6723 | pages = 165–9 | date = Mar 1999 | pmid = 10086359 | doi = 10.1038/18237 }}
*{{cite journal | author=Laurance ME, Kwok RP, Huang MS, ''et al.'' |title=Differential activation of viral and cellular promoters by human T-cell lymphotropic virus-1 tax and cAMP-responsive element modulator isoforms. |journal=J. Biol. Chem. |volume=272 |issue= 5 |pages= 2646-51 |year= 1997 |pmid= 9006899 |doi= }}
* {{cite journal | vauthors = Pati D, Meistrich ML, Plon SE | title = Human Cdc34 and Rad6B ubiquitin-conjugating enzymes target repressors of cyclic AMP-induced transcription for proteolysis | journal = Molecular and Cellular Biology | volume = 19 | issue = 7 | pages = 5001–13 | date = Jul 1999 | pmid = 10373550 | pmc = 84326 | doi =  10.1128/mcb.19.7.5001}}
*{{cite journal | author=Bonny C, Cooker LA, Goldberg E |title=Deoxyribonucleic acid-protein interactions and expression of the human testis-specific lactate dehydrogenase promoter: transcription factor Sp1 plays a major role. |journal=Biol. Reprod. |volume=58 |issue= 3 |pages= 754-9 |year= 1998 |pmid= 9510963 |doi= }}
* {{cite journal | vauthors = Inada A, Someya Y, Yamada Y, Ihara Y, Kubota A, Ban N, Watanabe R, Tsuda K, Seino Y | title = The cyclic AMP response element modulator family regulates the insulin gene transcription by interacting with transcription factor IID | journal = The Journal of Biological Chemistry | volume = 274 | issue = 30 | pages = 21095–103 | date = Jul 1999 | pmid = 10409662 | doi = 10.1074/jbc.274.30.21095 }}
*{{cite journal | author=Müller FU, Bokník P, Knapp J, ''et al.'' |title=Identification and expression of a novel isoform of cAMP response element modulator in the human heart. |journal=FASEB J. |volume=12 |issue= 12 |pages= 1191-9 |year= 1998 |pmid= 9737722 |doi=  }}
* {{cite journal | vauthors = Zauli G, Secchiero P, Rodella L, Gibellini D, Mirandola P, Mazzoni M, Milani D, Dowd DR, Capitani S, Vitale M | title = HIV-1 Tat-mediated inhibition of the tyrosine hydroxylase gene expression in dopaminergic neuronal cells | journal = The Journal of Biological Chemistry | volume = 275 | issue = 6 | pages = 4159–65 | date = Feb 2000 | pmid = 10660577 | doi = 10.1074/jbc.275.6.4159 }}
*{{cite journal | author=Fimia GM, De Cesare D, Sassone-Corsi P |title=CBP-independent activation of CREM and CREB by the LIM-only protein ACT. |journal=Nature |volume=398 |issue= 6723 |pages= 165-9 |year= 1999 |pmid= 10086359 |doi= 10.1038/18237 }}
*{{cite journal | author=Pati D, Meistrich ML, Plon SE |title=Human Cdc34 and Rad6B ubiquitin-conjugating enzymes target repressors of cyclic AMP-induced transcription for proteolysis. |journal=Mol. Cell. Biol. |volume=19 |issue= 7 |pages= 5001-13 |year= 1999 |pmid= 10373550 |doi=  }}
*{{cite journal | author=Inada A, Someya Y, Yamada Y, ''et al.'' |title=The cyclic AMP response element modulator family regulates the insulin gene transcription by interacting with transcription factor IID. |journal=J. Biol. Chem. |volume=274 |issue= 30 |pages= 21095-103 |year= 1999 |pmid= 10409662 |doi= }}
*{{cite journal | author=Zauli G, Secchiero P, Rodella L, ''et al.'' |title=HIV-1 Tat-mediated inhibition of the tyrosine hydroxylase gene expression in dopaminergic neuronal cells. |journal=J. Biol. Chem. |volume=275 |issue= 6 |pages= 4159-65 |year= 2000 |pmid= 10660577 |doi= }}
}}
{{refend}}
{{refend}}


== External links ==
== External links ==
* {{MeshName|CREM+protein,+human}}
* {{MeshName|CREM+protein,+human}}
* {{UCSC gene info|CREM}}


{{PDB Gallery|geneid=1390}}
{{Transcription factors|g1}}


{{protein-stub}}
{{NLM content}}
{{NLM content}}
{{Transcription factors}}
 
[[Category:Transcription factors]]
[[Category:Transcription factors]]
{{WikiDoc Sources}}

Latest revision as of 10:46, 16 May 2018

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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RefSeq (mRNA)

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View/Edit Human

cAMP responsive element modulator is a protein that in humans is encoded by the CREM gene,[1][2][3] and it belongs to the cAMP-responsive element binding protein family. It has multiple isoforms, which act either as repressors or activators.[4] CREB family is important for in regulating transcription in response to various stresses, metabolic and developmental signals.[5] CREM transcription factors also play an important role in many physiological systems, such as cardiac function,[6] circadian rhythms,[7] locomotion and spermatogenesis.[8]

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 transcriptnhunion.[3]

Gene location

The chromosomal location of CREM gene is 10p11.21, and it starts at 35415769 and ends at 35501886 bp from pter ( according to hg19-Feb_2009)[9]

Interactions

CAMP responsive element modulator has been shown to interact with FHL5.[10][11]

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.[12] 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[13]

Spermiogenesis deficiency

Like Dr. Paolo Sassone-Corsi wrote in this article CREM is “a master-switch regulator in testis”.[14] 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.[15] 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.[14]

Two studies proved that treat the rats with Salvia hypoleuca and Alpina galanga can significantly increased the CREM gene expression.[16][17]

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.[18]

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 3.0 3.1 "Entrez Gene: CREM cAMP responsive element modulator".
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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: official publication of the Federation of American Societies for Experimental Biology. 17 (2): 144–151. doi:10.1096/fj.01-0981com. ISSN 1530-6860. PMID 12554693.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ "CREM (cAMP responsive element modulator)". atlasgeneticsoncology.org. Retrieved 2016-10-16.
  10. ↑ 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.
  11. ↑ 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. doi:10.1038/18237. PMID 10086359.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 14.0 14.1 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.
  15. ↑ 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. doi:10.1038/380159a0. ISSN 0028-0836. PMID 8600390.
  16. ↑ 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.
  17. ↑ Mazaheri, Mahta; Shahdadi, Vahid; Nazari Boron, Ashraf (2016-10-16). "Molecullar and biochemical effect of alcohlic extract of Alpinia galanga on rat spermatogenesis process". Iranian Journal of Reproductive Medicine. 12 (11): 765–770. ISSN 1680-6433. PMC 4330656. PMID 25709632.
  18. ↑ 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.

Further reading

External links

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

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