CREBBP是抑癌基因，编码蛋白（CREB binding protein）是一种具有内源性组蛋白乙酰转移酶（HAT）活性的转录共激活因子，与共激活剂EP300有密切的同源性。CREBBP作为一个辅因子结合DNA结合蛋白，并起到支架的作用以募集一系列转录复合物组分。CREBBP本身可以补充基础转录机制，通过其HAT活性乙酰化赖氨酸尾巴，以改变染色质成一个更开放的构象激活转录。CREBBP的HAT活性也对非组蛋白有活性，包括肿瘤抑制因子如p53和组织特异性转录因子如GATA1。在白血病中，CREBBP与MOZ/KAT6A（赖氨酸乙酰转移酶6a）蛋白发生融合t（8；16）。CREBBP的体细胞突变在白血病、淋巴瘤和实体瘤（包括小细胞肺癌、鳞癌和膀胱癌）中被检测到。大多数CREBBP突变是截短型的，通常伴随着野生型等位基因的丢失，显示CREBBP是抑癌基因。CREBBP胚系突变可导致Rubinstein-Taybi综合征伴典型的面部和手指异常以及神经功能缺损。

CREBBP (CREB binding protein) is a transcriptional co-activator with intrinsic histone acetyltransferase (HAT) activity; it is closely homologous to the co-activator EP300. As a co-factor, CREBBP binds to DNA binding proteins where it functions as a scaffold to recruit a range of transcription complex components. CREBBP itself can recruit the basal transcriptional machinery, and through its HAT activity acetylate lysine tails to modify chromatin into a more open conformation for active transcription . The HAT activity of CREBBP is also active on non-histone proteins, including tumor suppressors such as p53 and tissue-specific transcription factors such as GATA1. In leukemias, CREBBP can be disrupted by translocations that fuse the HAT domain with the MOZ/KAT6A (lysine acetyltransferase 6a) protein t(8;16). Somatic mutations of CREBBP have been found in leukemia, lymphoma and solid tumors including small-cell lung cancer, squamous carcinoma and bladder cancer. Most CREBBP mutations are truncating and commonly co-occur with loss of the wildtype allele, suggesting that CREBBP is a tumor suppressor. Inherited mutations can result in the Rubinstein-Taybi syndrome with stereotypical facial and digit abnormalities along with neurological deficits. CREBBP-mutated tumors are dependent on EP300 activity and inhibitors targeting EP300 are efficacious in CREBBP-mutated cell line and mouse models.

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