CREB-binding protein; CBP transcriptional coactivator (CREBBP, CBP)
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Function
- binds to cAMP protein kinase phosphorylated form of CREB & interacts with at least one CREB family member as a specific DNA-bound complex
- intrinsic histone acetyltransferase (HAT) activity[3]
- acetylates histones, giving a specific tag for transcriptional activation[3]
- also acetylates non-histone proteins, including NCOA3 coactivator
- binds specifically to phosphorylated CREB & enhances its transcriptional activity toward cAMP-responsive genes
- binds to cAMP protein kinase phosphorylated form of CREB & interacts with at least one CREB family member as a specific DNA-bound complex
- methylation of the KIX domain by CARM1 blocks association with CREB; this results in the blockade of CREB signaling, & in activation of apoptotic response (putative)
- phosphorylated upon DNA damage, probably by ATM or ATR
- sumoylation negatively regulates transcriptional activity via recruitment of DAAX (putative)
- found in a complex containing NCOA2; NCOA3; IKKA; IKKB & IKBKG
- probably part of a complex with HIF1A & EP300
- interacts with phosphorylated CREB1
- interacts with the C-terminal region of CITED4
- the TAZ-type 1 domain interacts with HIF1A
- interacts with MAF, SRCAP, CARM1, ELF3, MLLT7/FOXO4, N4BP2, NCOA1, NCOA3, NCOA6, PCAF, PELP1, PML, SMAD1, SMAD2, SMAD3, SPIB & TRERF1
- interacts with KLF1; the interaction results in acetylation of KLF1 & enhancement of its transcriptional activity
- interacts with ZCCHC12 (putative)
- interacts with DAXX; the interaction is dependent on CBP sumoylation & results in suppression of the transcriptional activiy via recruitment of HDAC2 to DAAX
- interacts with MTDH
- interacts with NFATC4
- interacts with MAFG; the interaction acetylates MAFG in the basic region & stimulates NFE2 transcriptional activity through increasing its DNA-binding activity
- interacts with IRF2; the interaction acetylates IRF2 & regulates its activity on the H4 promoter
- interacts with TFIIB
Structure
- the KIX domain mediates binding to HIV-1 Tat
- contains 1 bromo domain
- contains 1 KIX domain
- contains 2 TAZ-type Zn+2 fingers
- contains 1 ZZ-type Zn+2 finger
Compartment
Pathology
- binding of adenovirus E1a oncoprotein inhibits activity (does not disrupt histone acetyltransferase activity)
- loss of heterozygosity described in 80% of glioblastomas[4]
- loss of heterozygocity around CBP gene locus seen in hepatocellular carcinoma
- chromosomal translocations in acute leukemia
- mutations associated with Rubinstein-Taybi syndrome
- interacts with HTLV-1 Tax & p30II
- interacts with HIV-1 Tat
More general terms
- transcriptional adaptor protein; transcriptional coactivator
- histone acetyltransferase
- zinc finger protein
- phosphoprotein
Additional terms
- histone acetyltransferase p300; p300 HAT; E1A-associated protein p300 (EP300, P300)
- IkB kinase complex
References
- ↑ Arany Z et al A family of transcriptional adaptor proteins targeted by the E1A oncoprotein. Nature 374:81 1995 PMID: https://www.ncbi.nlm.nih.gov/pubmed/7870178
- ↑ Lundblad JR et al Adenoviral E1A-associated protein p300 as a functional homologue of the transcriptional co-activator CBP. Nature 374:85 1995 PMID: https://www.ncbi.nlm.nih.gov/pubmed/7870179
- ↑ 3.0 3.1 3.2 Bannister AJ & Kouzarides T The CBP co-activator is a histone acetyltransferase. Nature 384:641-3 1996 PMID: https://www.ncbi.nlm.nih.gov/pubmed/8967953
- ↑ 4.0 4.1 Marks P et al Histone deacetylases and cancer: causes and therapies. Nature Reviews Cancer 1:194-202, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11902574
- ↑ UniProt http://www.uniprot.org/uniprot/Q92793.html
- ↑ Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/CBPID42.html
- ↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=CREBBP
- ↑ Wikipedia; Note: P300/CBP entry http://en.wikipedia.org/wiki/P300/CBP