サイクリックAMP応答配列結合タンパク質、サイクリックAMP応答エレメント結合タンパク質

関: cAMP response element-binding protein、CRE-binding protein、CREB、CREB protein

WordNet

a straight line that generates a cylinder or cone
one of four substances thought in ancient and medieval cosmology to constitute the physical universe; "the alchemists believed that there were four elements"
the situation in which you are happiest and most effective; "in your element"
the most favorable environment for a plant or animal; "water is the element of fishes"
executed with proper legal authority; "a binding contract"
the protective covering on the front, back, and spine of a book; "the book had a leather binding" (同)book binding, cover, back
strip sewn over or along an edge for reinforcement or decoration
the capacity to attract and hold something
a result; "this situation developed in response to events in Africa"
a phrase recited or sung by the congregation following a versicle by the priest or minister
the manner in which an electrical or mechanical device responds to an input signal or a range of input signals
of a compound having atoms arranged in a ring structure
recurring in cycles (同)cyclical
conforming to the Carnot cycle
forming a whorl or having parts arranged in a whorl; "cyclic petals"; "cyclic flowers"
marked by repeated cycles
any of a large group of nitrogenous organic compounds that are essential constituents of living cells; consist of polymers of amino acids; essential in the diet of animals for growth and for repair of tissues; can be obtained from meat and eggs and milk and legumes; "a diet high in protein"

PrepTutorEJDIC

〈C〉(物質を構成する)元素 / 〈C〉《修飾語[句]を伴って》(…の)(基本的な)『要素』,『成分』;《しばしば複数形で》構成分子 / 〈C〉(生物に固有の)生息場所,環境;(人の)適所,本領 / 〈C〉《古》四大(しだい)[元素](自然界の基本的構成要素と考えられていた地(earth)・水(water)・風(air)・火(fire)の4大要素の一つ) / 《the elements》(雨・風・雪などの)自然力・風雨,(特に)悪天候 / 《the elements》(学問の)原理,初歩,概論
義務的な,拘束力ある / 〈U〉しばること;〈C〉しばる物 / 〈C〉製本,装丁 / 〈U〉縁(‘ふち')取り材料
〈C〉(…に対する)『返事』,『返答』《+『to』+『名』》 / 〈C〉〈U〉(…に対する)『反応』,『反響』《『to』+『名』》 / 〈C〉応答歌,応唱(牧師にならって合唱隊・会衆が短い祈り・歌を応答すること)
蛋白(たんばく)質

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/06/21 01:00:00」(JST)

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[Wiki en表示]

CREB (top) is a transcription factor capable of binding DNA (bottom) and regulating gene expression.

CREB (cAMP response element-binding protein)^[1] is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the downstream genes.^[2] CREB was first described in 1987 as a cAMP-responsive transcription factor regulating the somatostatin gene.^[3]

Genes whose transcription is regulated by CREB include: c-fos, the neurotrophin BDNF (brain-derived neurotrophic factor), tyrosine hydroxylase, and many neuropeptides (such as somatostatin, enkephalin, VGF, and corticotropin-releasing hormone).^[2]

CREB is closely related in structure and function to CREM (cAMP response element modulator) and ATF-1 (activating transcription factor-1) proteins. CREB proteins are expressed in many animals, including humans.

CREB has a well-documented role in neuronal plasticity and long-term memory formation in the brain.^[4] CREB has been shown to be integral in the formation of spatial memory. In recent experiments it has been demonstrated that CREB may possess therapeutic potential for patients that have Alzheimer's disease.^[5]

Subtypes

The following genes encode CREB or CREB-like proteins:

CREB1 (CREB1)
CREB2 renamed ATF4 (ATF4)
CREB3 (CREB3)
CREB5 (CREB5)
CREB3L1 (CREB3L1)
CREB3L2 (CREB3L2)
CREB3L3 (CREB3L3)
CREB3L4 (CREB3L4)

Structure

General structure of the CREB protein.

When activated CREB protein forms a dimer and binds to the CRE region of DNA. Hydrophobic leucine amino acids are located along the inner edge of the alpha helix. These leucine residues tightly bind to leucine residues of another CREB protein forming the dimer. This chain of leucine residues forms the leucine zipper motif. The protein also has a magnesium ion that facilitates binding to DNA.

Mechanism of action

A typical (albeit somewhat simplified) sequence of events is as follows: A signal arrives at the cell surface, activates the corresponding receptor, which leads to the production of a second messenger such as cAMP or Ca²⁺, which in turn activates a protein kinase. This protein kinase translocates to the cell nucleus, where it activates a CREB protein. The activated CREB protein then binds to a CRE region, and is then bound to by a CBP (CREB-binding protein), which coactivates it, allowing it to switch certain genes on or off. The DNA binding of CREB is mediated via its basic leucine zipper domain (bZIP domain) as depicted in the image.

Function

CREB has many functions in many different organs, and some of its functions have been studied in relation to the brain.^[6] CREB proteins in neurons are thought to be involved in the formation of long-term memories; this has been shown in the marine snail Aplysia, the fruit fly Drosophila melanogaster, in rats and in mice (see CREB in Molecular and Cellular Cognition).^[1] CREB is necessary for the late stage of long-term potentiation. CREB also has an important role in the development of drug addiction.^[7]^[8]^[9] There are activator and repressor forms of CREB. Flies genetically engineered to overexpress the inactive form of CREB lose their ability to retain long-term memory. CREB is also important for the survival of neurons, as shown in genetically engineered mice, where CREB and CREM were deleted in the brain. If CREB is lost in the whole developing mouse embryo, the mice die immediately after birth, again highlighting the critical role of CREB in promoting survival.

Disease linkage

Disturbance of CREB function in brain can contribute to the development and progression of Huntington's Disease. Abnormalities of a protein that interacts with the KID domain of CREB, the CREB-binding protein, (CBP) is associated with Rubinstein-Taybi syndrome. CREB is also thought to be involved in the growth of some types of cancer.

cAMP response element

The cAMP response element is the response element for CREB. Since the effects of protein kinase A on the synthesis of proteins work by activating CREB, the cAMP response element is responsible for modulating the effects of protein kinase A that work by protein synthesis.

References

^ ^a ^b Bourtchuladze et al. "Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein." Cell 79(1):59-68
^ ^a ^b Purves, Dale, George J. Augustine, David Fitzpatrick, William C. Hall, Anthony-Samuel LaMantia, James O. McNamara, and Leonard E. White (2008). Neuroscience. 4th ed. Sinauer Associates. pp. 170–6. ISBN 978-0-87893-697-7.
^ Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene. Montminy MR and Bilezikjian LM. Nature. 1987 Jul 9-15;328(6126):175-8.
^ Silva et al. "CREB and Memory", Annual Review of Neuroscience, 21:127-148
^ Downregulation of CREB expression in Alzheimer’s brain and in Ab-treated rat hippocampal neurons
^ Carlezon WA, Duman RS, Nestler EJ (August 2005). "The many faces of CREB". Trends in Neurosciences 28 (8): 436–45. doi:10.1016/j.tins.2005.06.005. PMID 15982754.
^ Nazarian A, Sun WL, Zhou L, Kemen LM, Jenab S, Quinones-Jenab V (April 2009). "Sex differences in basal and cocaine-induced alterations in PKA and CREB proteins in the nucleus accumbens". Psychopharmacology 203 (3): 641–50. doi:10.1007/s00213-008-1411-5. PMID 19052730.
^ Wang Y, Ghezzi A, Yin JC, Atkinson NS (June 2009). "CREB regulation of BK channel gene expression underlies rapid drug tolerance". Genes, Brain, and Behavior 8 (4): 369–76. doi:10.1111/j.1601-183X.2009.00479.x. PMC 2796570. PMID 19243452.
^ DiRocco DP, Scheiner ZS, Sindreu CB, Chan GC, Storm DR (February 2009). "A role for calmodulin-stimulated adenylyl cyclases in cocaine sensitization". Journal of Neuroscience 29 (8): 2393–403. doi:10.1523/JNEUROSCI.4356-08.2009. PMC 2678191. PMID 19244515.

Bibliography

Lauren Slater, (2005). Opening Skinner's Box: Great Psychological Experiments of the Twentieth Century. New York: W. W. Norton & Company. ISBN 0-393-32655-1.
Barco A, Bailey C, Kandel E (2006). "Common molecular mechanisms in explicit and implicit memory". J. Neurochem. 97 (6): 1520–33. doi:10.1111/j.1471-4159.2006.03870.x. PMID 16805766.
Conkright M, Montminy M (2005). "CREB: the unindicted cancer co-conspirator". Trends Cell Biol. 15 (9): 457–9. doi:10.1016/j.tcb.2005.07.007. PMID 16084096.
Mantamadiotis T, Lemberger T, Bleckmann S, Kern H, Kretz O, Martin Villalba A, Tronche F, Kellendonk C, Gau D, Kapfhammer J, Otto C, Schmid W, Schütz G (2002). "Disruption of CREB function in brain leads to neurodegeneration". Nat. Genet. 31 (1): 47–54. doi:10.1038/ng882. PMID 11967539.
Mayr B, Montminy M (2001). "Transcriptional regulation by the phosphorylation-dependent factor CREB". Nat. Rev. Mol. Cell Biol. 2 (8): 599–609. doi:10.1038/35085068. PMID 11483993.
Yin J, Del Vecchio M, Zhou H, Tully T (1995). "CREB as a memory modulator: induced expression of a dCREB2 activator isoform enhances long-term memory in Drosophila". Cell 81 (1): 107–15. doi:10.1016/0092-8674(95)90375-5. PMID 7720066.
Yin J, Wallach J, Del Vecchio M, Wilder E, Zhou H, Quinn W, Tully T (1994). "Induction of a dominant negative CREB transgene specifically blocks long-term memory in Drosophila". Cell 79 (1): 49–58. doi:10.1016/0092-8674(94)90399-9. PMID 7923376.

External links

Johannessen, M., Pedersen Delghandi, M., and Moens, U. (2004) - What Turns CREB on ? - Cell Signall.; 10:1211-1227. http://www.sigtrans.org/publications/what-turns-creb-on/
http://focus.hms.harvard.edu/2001/Oct26_2001/neuroscience.html
CREB Protein at the US National Library of Medicine Medical Subject Headings (MeSH)
Drosophila Cyclic-AMP response element binding protein A - The Interactive Fly
Drosophila Cyclic-AMP response element binding protein B at 17A - The Interactive Fly

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「サイクリックAMP応答配列結合タンパク質」

　　[★]

英: cyclic AMP response element-binding protein、cAMP response element-binding protein、CRE-binding protein、CREB protein、CREB
関: cAMP応答配列結合タンパク質、CRE結合タンパク質、サイクリックAMP応答エレメント結合タンパク質

「cAMP response element-binding protein」

　　[★]

cAMP応答配列結合タンパク質、サイクリックAMP応答配列結合タンパク質

関: CRE-binding protein、CREB、CREB protein、cyclic AMP response element-binding protein

「CREB protein」

　　[★]

サイクリックAMP応答配列結合タンパク質

関: cAMP response element-binding protein、CRE-binding protein、CREB、cyclic AMP response element-binding protein

「サイクリックAMP応答エレメント結合タンパク質」

　　[★]

英: cyclic AMP response element-binding protein
関: cAMP応答配列結合タンパク質、サイクリックAMP応答配列結合タンパク質

「cyclic AMP response element-binding protein A」

　　[★]

サイクリックAMP応答配列結合タンパク質A

「binding」

　　[★]

n.

結合、バインディング

adj.

結合性の

関: affinity、associate、bind、bond、bonding、combine、conjoin、conjugate、conjugation、conjunction、connect、connection、connective、connectivity、couple、dock、engage、engagement、join、ligate、linkage、symphysial、symphysic、union

「element」

　　[★]

n.

要素、成分、素。(構成)分子。(科学)元素、(数)(集合の)要素、元素、素。(行列の)要素、成分。(図形を火ｔが千都来る)要素。(文法の)要素
(電子)素子、(光学)素子

関: basal、bases、basic、basis、component、composition、constituent、elementary、factor、fundamentals、ingredient、moiety

「cyclic」

　　[★]

adj.

環状の、環式の、周期性の、サイクリック

関: annular、circular、cyclical、cyclicity、cyclo、periodic、periodicity

「binding protein」

　　[★]

結合タンパク質、結合タンパク、結合蛋白質、結合蛋白

関: BP、carrier protein、transport protein

「response」

　　[★]

n.

返答、応答
反応、感応、反響。(刺激に対する)反応

[ReferenceA-1] Bourtchuladze et al. "Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein." Cell 79(1):59-68

[Purves-2] Purves, Dale, George J. Augustine, David Fitzpatrick, William C. Hall, Anthony-Samuel LaMantia, James O. McNamara, and Leonard E. White (2008). Neuroscience. 4th ed. Sinauer Associates. pp. 170–6. ISBN 978-0-87893-697-7.

[3] Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene. Montminy MR and Bilezikjian LM. Nature. 1987 Jul 9-15;328(6126):175-8.

[4] Silva et al. "CREB and Memory", Annual Review of Neuroscience, 21:127-148

[5] Downregulation of CREB expression in Alzheimer’s brain and in Ab-treated rat hippocampal neurons

[pmid15982754-6] Carlezon WA, Duman RS, Nestler EJ (August 2005). "The many faces of CREB". Trends in Neurosciences 28 (8): 436–45. doi:10.1016/j.tins.2005.06.005. PMID 15982754.

[pmid19052730-7] Nazarian A, Sun WL, Zhou L, Kemen LM, Jenab S, Quinones-Jenab V (April 2009). "Sex differences in basal and cocaine-induced alterations in PKA and CREB proteins in the nucleus accumbens". Psychopharmacology 203 (3): 641–50. doi:10.1007/s00213-008-1411-5. PMID 19052730.

[pmid19243452-8] Wang Y, Ghezzi A, Yin JC, Atkinson NS (June 2009). "CREB regulation of BK channel gene expression underlies rapid drug tolerance". Genes, Brain, and Behavior 8 (4): 369–76. doi:10.1111/j.1601-183X.2009.00479.x. PMC 2796570. PMID 19243452.

[pmid19244515-9] DiRocco DP, Scheiner ZS, Sindreu CB, Chan GC, Storm DR (February 2009). "A role for calmodulin-stimulated adenylyl cyclases in cocaine sensitization". Journal of Neuroscience 29 (8): 2393–403. doi:10.1523/JNEUROSCI.4356-08.2009. PMC 2678191. PMID 19244515.

リンク元	「サイクリックAMP応答配列結合タンパク質」「cAMP response element-binding protein」「CREB protein」「サイクリックAMP応答エレメント結合タンパク質」
拡張検索	「cyclic AMP response element-binding protein A」
関連記事	「binding」「element」「cyclic」「binding protein」「response」

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案内

cyclic AMP response element-binding protein