# CREB-bindingseiwit

Het CREB-bindingseiwit (CREB-Binding-Protein, afgekort CBP), is een co-activator bij de transcriptie.
Bij de mens wordt het CREB-bindingseiwit gecodeerd door het CREBBP-gen (ook wel CBP-gen genoemd).
Het CREB-bindingseiwit heeft de volgende domeinen:
* het nucleusreceptor interactie domein (RID),
* het CREB en MYB interactie domein (KIX),
* de cysteïne/histidine regio's (TAZ1/CH1 en TAZ2/CH3) en
* het interferon reactiebindend domein (IBiD).
De CREB-bindingseiwit domeinen, KIX, TAZ1 en TAZ2 binden elk stevig aan de beide transactivatie domeinen 9aaTADs van de transcriptiefactor p53.

## Functie

Het CREBBP-gen is betrokken bij de transcriptionele coactivatie van veel verschillende transcriptiefactoren. Het werd voor het eerst geïsoleerd als een nucleuseiwit dat zich bindt aan het cAMP-reactie-elementbindend eiwit (CREB). Het gen speelt een kritische rol bij de embryonale ontwikkeling, controle van de groei en homeostase door te koppelen aan chromatine en het zo geschikt te maken voor de herkenning van de transcriptiefactor. Het door het gen gecodeerde eiwit heeft een eigen histon-acetyltransferase activiteit en werkt ook ondersteunend voor het stabiliseren van bijkomende eiwitinteracties met het transcriptieomplex. Het eiwit acetyleert zowel histonen als non-histon eiwitten. Het eiwit heeft zeer sterk vergelijkbare regio's met het eiwit EP300 en hun bromodomein, cysteïne-histidine-rijke regio's en het histonacetyltransferasedomein.

## Klinisch belang

Mutaties in het CREBBP-gen is de oorzaak van het syndroom van Rubinstein-Taybi (RTS). De chromosomale translocatie, waarbij het CREBBP-gen betrokken is, wordt in verband gebracht met acute myeloïde leukemie.

## Interacties

Het CREB-bindingseiwit vertoont interactie met de volgende eiwitten:
| Activating transcription factor 2 Androgen receptor Autoimmune regulator BRCA1 BRCA2 C-jun C-src tyrosine kinase Casein kinase 2, alpha 1 Ccaat-enhancer-binding proteins CDX2 CREB1 CSNK2A2 CUTL1 Cyclin-dependent kinase 8 | EBF1 Estrogen receptor alpha EVI1 FOXO1 GLI3 Glucocorticoid receptor Hepatocyte nuclear factor 4 alpha HIF1A HIPK2 HNF1A HOXB7 ING1 KHDRBS1 KLF13 | KLF4 Ku70 MAF MLL Mothers against decapentaplegic homolog 1 MSX1 MYB MYBL2 MyoD NCOA6 NEUROG1 NFATC4 NFE2 NFE2L2 | Nuclear receptor coactivator 1 Nuclear receptor coactivator 3 NUP98 P53 PCAF POLR2A PPARGC1A Promyelocytic leukemia protein PTMA RBBP4 RELA RPS6KA3 SERTAD1 Serum response factor | SMARCB1 SMARCA4 SREBF1 SREBF2 SS18L1 STAT1 STAT2 STAT6 TCF3 TGS1 Thymine-DNA glycosylase Transcription Factor II B TRERF1 Zif268. |
* ↑ Chrivia JC, Kwok RP, Lamb N, Hagiwara M, Montminy MR, Goodman RH (October 1993). Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 365 (6449): 855–9. PMID 8413673. DOI: 10.1038/365855a0.
* ↑ Wydner KL, Bhattacharya S, Eckner R, Lawrence JB, Livingston DM (November 1995). Localization of human CREB-binding protein gene (CREBBP) to 16p13.2-p13.3 by fluorescence in situ hybridization. Genomics 30 (2): 395–6. PMID 8586450.
* ↑ Teufel DP, Freund SM, Bycroft M, Fersht AR (April 2007). Four domains of p300 each bind tightly to a sequence spanning both transactivation subdomains of p53. PNAS 104 (17): 7009–7014. PMID 17438265. PMC 1855428. DOI: 10.1073/pnas.0702010104. ; Piskacek S, Gregor M, Nemethova M, Grabner M, Kovarik P, Piskacek M (June 2007). Nine-amino-acid transactivation domain: establishment and prediction utilities. Genomics 89 (6): 756–68. PMID 17467953. DOI: 10.1016/j.ygeno.2007.02.003. ; Piskacek M (5 november 2009). 9aaTAD is a common transactivation domain recruits multiple general coactivators TAF9, MED15, CBP/p300 and GCN5. Nature Precedings Pre-publication. DOI: 10.1038/npre.2009.3488.2. ; Piskacek M (5 november 2009). 9aaTADs mimic DNA to interact with a pseudo-DNA Binding Domain KIX of Med15 (Molecular Chameleons). Nature Precedings Pre-publication. DOI: 10.1038/npre.2009.3939.1. ; Piskacek M (20 november 2009). 9aaTAD Prediction result (2006). Nature Precedings Pre-publication. DOI: 10.1038/npre.2009.3984.1.
* ↑ The prediction for 9aaTADs (for both acidic and hydrophilic transactivation domains) is available online from ExPASy https://web.archive.org/web/20100716130743/http://us.expasy.org/tools/ and EMBnet Spain https://archive.today/20130704002729/http://www.es.embnet.org/Services/EMBnetAT/htdoc/9aatad/
* ↑ Ogryzko VV et al. "The transcriptional coactivators p300 and CBP are histone acetyltransferases". Cell. 1996 87(5):953-9.. Gearchiveerd op 19 maart 2020.
* 1 2 Entrez Gene: CREBBP (CREB-binding protein).
* ↑ Petrij F, Giles RH, Dauwerse HG, Saris JJ, Hennekam RC, Masuno M, Tommerup N, van Ommen GJ, Goodman RH, Peters DJ (July 1995). Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature 376 (6538): 348–51. PMID 7630403. DOI: 10.1038/376348a0.
* ↑ Vizmanos JL, Larráyoz MJ, Lahortiga I, Floristán F, Alvarez C, Odero MD, Novo FJ, Calasanz MJ (April 2003). t(10;16)(q22;p13) and MORF-CREBBP fusion is a recurrent event in acute myeloid leukemia. Genes Chromosomes Cancer 36 (4): 402–5. PMID 12619164. DOI: 10.1002/gcc.10174.
* 1 2 3 Sano, Y, Tokitou F, Dai P, Maekawa T, Yamamoto T, Ishii S (Oct. 1998). CBP alleviates the intramolecular inhibition of ATF-2 function. J. Biol. Chem. 273 (44): 29098–105 (UNITED STATES)​. ISSN: 0021-9258. PMID 9786917. DOI: 10.1074/jbc.273.44.29098.
* 1 2 Kim, J, Jia L, Stallcup M R, Coetzee G A (Feb. 2005). The role of protein kinase A pathway and cAMP responsive element-binding protein in androgen receptor-mediated transcription at the prostate-specific antigen locus. J. Mol. Endocrinol. 34 (1): 107–18 (England)​. ISSN: 0952-5041. PMID 15691881. DOI: 10.1677/jme.1.01701.
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* ↑ Iioka, Takashi, Furukawa Keizo, Yamaguchi Akira, Shindo Hiroyuki, Yamashita Shunichi, Tsukazaki Tomoo (Aug. 2003). P300/CBP acts as a coactivator to cartilage homeoprotein-1 (Cart1), paired-like homeoprotein, through acetylation of the conserved lysine residue adjacent to the homeodomain. J. Bone Miner. Res. 18 (8): 1419–29 (United States)​. ISSN: 0884-0431. PMID 12929931. DOI: 10.1359/jbmr.2003.18.8.1419.
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* ↑ Pao, G M, Janknecht R, Ruffner H, Hunter T, Verma I M (Feb. 2000). CBP/p300 interact with and function as transcriptional coactivators of BRCA1. Proc. Natl. Acad. Sci. U.S.A. 97 (3): 1020–5 (UNITED STATES)​. ISSN: 0027-8424. PMID 10655477. PMC 15508. DOI: 10.1073/pnas.97.3.1020.
* ↑ Chai, Y L, Cui J, Shao N, Shyam E, Reddy P, Rao V N (Jan. 1999). The second BRCT domain of BRCA1 proteins interacts with p53 and stimulates transcription from the p21WAF1/CIP1 promoter. Oncogene 18 (1): 263–8 (ENGLAND)​. ISSN: 0950-9232. PMID 9926942. DOI: 10.1038/sj.onc.1202323.
* ↑ Benezra, Miriam, Chevallier Nathalie, Morrison Debra J, MacLachlan Timothy K, El-Deiry Wafik S, Licht Jonathan D (Jul. 2003). BRCA1 augments transcription by the NF-kappaB transcription factor by binding to the Rel domain of the p65/RelA subunit. J. Biol. Chem. 278 (29): 26333–41 (United States)​. ISSN: 0021-9258. PMID 12700228. DOI: 10.1074/jbc.M303076200.
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* ↑ Kovacs KA, Steinmann M, Magistretti PJ, Halfon O, Cardinaux JR (Sept. 2003). CCAAT/enhancer-binding protein family members recruit the coactivator CREB-binding protein and trigger its phosphorylation. J Biol. Chem. 278 (38): 36959–65 (UNITED STATES)​. ISSN: 0021-9258. PMID 12857754. DOI: 10.1074/jbc.M303147200.
* ↑ Lorentz, O, Suh E R, Taylor J K, Boudreau F, Traber P G (Mar. 1999). CREB-binding [corrected protein interacts with the homeodomain protein Cdx2 and enhances transcriptional activity]. J. Biol. Chem. 274 (11): 7196–9 (UNITED STATES)​. ISSN: 0021-9258. PMID 10066780. DOI: 10.1074/jbc.274.11.7196.
* ↑ Shi, Yuling, Venkataraman Sujatha L, Dodson Gerald E, Mabb Angela M, LeBlanc Scott, Tibbetts Randal S (Apr. 2004). Direct regulation of CREB transcriptional activity by ATM in response to genotoxic stress. Proc. Natl. Acad. Sci. U.S.A. 101 (16): 5898–903 (United States)​. ISSN: 0027-8424. PMID 15073328. PMC 395895. DOI: 10.1073/pnas.0307718101.
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* ↑ Radhakrishnan, I, Pérez-Alvarado G C, Parker D, Dyson H J, Montminy M R, Wright P E (Dec. 1997). Solution structure of the KIX domain of CBP bound to the transactivation domain of CREB: a model for activator:coactivator interactions. Cell 91 (6): 741–52 (UNITED STATES)​. ISSN: 0092-8674. PMID 9413984. DOI: 10.1016/S0092-8674(00)80463-8.
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