Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
Cancer Research Institute, Basic School of Medicine, Central South University, Changsha, 410078, Hunan, China.
Cell Mol Biol Lett. 2024 Nov 14;29(1):141. doi: 10.1186/s11658-024-00661-y.
HBO1, also known as KAT7 or MYST2, is a crucial histone acetyltransferase with diverse cellular functions. It typically forms complexes with protein subunits or cofactors such as MEAF6, ING4, or ING5, and JADE1/2/3 or BRPF1/2/3, where the BRPF or JADE proteins serve as the scaffold targeting histone H3 or H4, respectively. The histone acetylation mediated by HBO1 plays significant roles in DNA replication and gene expression regulation. Additionally, HBO1 catalyzes the modification of proteins through acylation with propionyl, butyryl, crotonyl, benzoyl, and acetoacetyl groups. HBO1 undergoes ubiquitination and degradation by two types of ubiquitin complexes and can also act as an E3 ubiquitin ligase for the estrogen receptor α (ERα). Moreover, HBO1 participates in the expansion of medullary thymic epithelial cells (mTECs) and regulates the expression of peripheral tissue genes (PTGs) mediated by autoimmune regulator (AIRE), thus inducing immune tolerance. Furthermore, HBO1 influences the renewal of hematopoietic stem cells and the development of neural stem cells significantly. Importantly, the overexpression of HBO1 in various cancers suggests its carcinogenic role and potential as a therapeutic target. This review summarizes recent advancements in understanding HBO1's involvement in acylation modification, DNA replication, ubiquitination, immunity, and stem cell renewal.
HBO1,也称为 KAT7 或 MYST2,是一种重要的组蛋白乙酰转移酶,具有多种细胞功能。它通常与蛋白质亚基或辅助因子形成复合物,如 MEAF6、ING4、ING5、JADE1/2/3 或 BRPF1/2/3,其中 BRPF 或 JADE 蛋白分别作为靶向组蛋白 H3 或 H4 的支架。HBO1 介导的组蛋白乙酰化在 DNA 复制和基因表达调控中起着重要作用。此外,HBO1 通过丙酰化、丁酰化、巴豆酰化、苯甲酰化和乙酰乙酰化修饰蛋白质。HBO1 可以通过两种泛素化复合物进行泛素化和降解,也可以作为雌激素受体α(ERα)的 E3 泛素连接酶。此外,HBO1 参与髓质胸腺上皮细胞(mTEC)的扩张,并调节自身免疫调节因子(AIRE)介导的外周组织基因(PTGs)的表达,从而诱导免疫耐受。此外,HBO1 显著影响造血干细胞的更新和神经干细胞的发育。重要的是,HBO1 在各种癌症中的过度表达表明其致癌作用和作为治疗靶点的潜力。本综述总结了 HBO1 在酰化修饰、DNA 复制、泛素化、免疫和干细胞更新方面的最新研究进展。