CREBBP is an acetyltransferase enzyme that acetylates histones, giving a specific tag for transcriptional activation. It also acetylates non-histone proteins, like NCOA3 coactivator. This protein mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. CBP, as coactivator, augments the activity of phosphorylated CREB to activate transcription of cAMP-responsive genes. Chromosomal aberrations involving CREBBP may be a cause of acute myeloid leukemias. For example, MYST3-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription. Defects in CREBBP are also the cause of Rubinstein-Taybi syndrome (RSTS). RSTS is an autosomal dominant disorder characterized by craniofacial abnormalities, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies.
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