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:
Bronnen, noten en/of referenties
- ↑ 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://web.archive.org/web/20220618043310/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).
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