Zhu Yu, Wang Zi, Li Yanan, Peng Hongling, Liu Jing, Zhang Ji, Xiao Xiaojuan
Department of Hematology, The Second Xiangya Hospital, Molecular Biology Research Center, School of Life Sciences, Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University, Changsha 410011, China.
The Affiliated Nanhua Hospital, Department of Clinical Laboratory, Hengyang Medical School, University of South China, Hengyang 421001, China.
Cancers (Basel). 2023 Feb 14;15(4):1219. doi: 10.3390/cancers15041219.
Disordered histone acetylation has emerged as a key mechanism in promoting hematological malignancies. CREB-binding protein (CREBBP) and E1A-binding protein P300 (EP300) are two key acetyltransferases and transcriptional cofactors that regulate gene expression by regulating the acetylation levels of histone proteins and non-histone proteins. dysregulation and CREBBP/EP300-containing complexes are critical for the initiation, progression, and chemoresistance of hematological malignancies. CREBBP/EP300 also participate in tumor immune responses by regulating the differentiation and function of multiple immune cells. Currently, CREBBP/EP300 are attractive targets for drug development and are increasingly used as favorable tools in preclinical studies of hematological malignancies. In this review, we summarize the role of CREBBP/EP300 in normal hematopoiesis and highlight the pathogenic mechanisms of CREBBP/EP300 in hematological malignancies. Moreover, the research basis and potential future therapeutic implications of related inhibitors were also discussed from several aspects. This review represents an in-depth insight into the physiological and pathological significance of CREBBP/EP300 in hematology.
组蛋白乙酰化紊乱已成为促进血液系统恶性肿瘤发生的关键机制。CREB结合蛋白（CREBBP）和E1A结合蛋白P300（EP300）是两种关键的乙酰转移酶和转录辅因子，它们通过调节组蛋白和非组蛋白的乙酰化水平来调控基因表达。CREBBP/EP300的失调以及包含它们的复合物对于血液系统恶性肿瘤的起始、进展和化疗耐药性至关重要。CREBBP/EP300还通过调节多种免疫细胞的分化和功能参与肿瘤免疫反应。目前，CREBBP/EP300是药物研发的有吸引力的靶点，并越来越多地被用作血液系统恶性肿瘤临床前研究的有利工具。在这篇综述中，我们总结了CREBBP/EP300在正常造血中的作用，并强调了CREBBP/EP300在血液系统恶性肿瘤中的致病机制。此外，还从几个方面讨论了相关抑制剂的研究基础及其潜在的未来治疗意义。这篇综述深入洞察了CREBBP/EP300在血液学中的生理和病理意义。
