Suppr超能文献

HBO1,一个神秘的 KAT 及其与癌症的联系。

HBO1, a MYSTerious KAT and its links to cancer.

机构信息

Tsuruoka Metabolomics Laboratory, National Cancer Center, Tsuruoka, Yamagata 997-0052, Japan.

Department of Molecular Biology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan.

出版信息

Biochim Biophys Acta Gene Regul Mech. 2024 Sep;1867(3):195045. doi: 10.1016/j.bbagrm.2024.195045. Epub 2024 Jun 6.

Abstract

The histone acetyltransferase HBO1, also known as KAT7, is a major chromatin modifying enzyme responsible for H3 and H4 acetylation. It is found within two distinct tetrameric complexes, the JADE subunit-containing complex and BRPF subunit-containing complex. The HBO1-JADE complex acetylates lysine 5, 8 and 12 of histone H4, and the HBO1-BRPF complex acetylates lysine 14 of histone H3. HBO1 regulates gene transcription, DNA replication, DNA damage repair, and centromere function. It is involved in diverse signaling pathways and plays crucial roles in development and stem cell biology. Recent work has established a strong relationship of HBO1 with the histone methyltransferase MLL/KMT2A in acute myeloid leukemia. Here, we discuss functional and pathological links of HBO1 to cancer, highlighting the underlying mechanisms that may pave the way to the development of novel anti-cancer therapies.

摘要

组蛋白乙酰转移酶 HBO1,也称为 KAT7,是一种主要的染色质修饰酶,负责 H3 和 H4 的乙酰化。它存在于两个不同的四聚体复合物中,JADE 亚基包含的复合物和 BRPF 亚基包含的复合物。HBO1-JADE 复合物乙酰化组蛋白 H4 的赖氨酸 5、8 和 12,而 HBO1-BRPF 复合物乙酰化组蛋白 H3 的赖氨酸 14。HBO1 调节基因转录、DNA 复制、DNA 损伤修复和着丝粒功能。它参与多种信号通路,在发育和干细胞生物学中发挥关键作用。最近的工作已经确立了 HBO1 与急性髓系白血病中的组蛋白甲基转移酶 MLL/KMT2A 之间的紧密关系。在这里,我们讨论了 HBO1 与癌症的功能和病理联系,强调了可能为开发新型抗癌疗法铺平道路的潜在机制。

相似文献

1
HBO1, a MYSTerious KAT and its links to cancer.
Biochim Biophys Acta Gene Regul Mech. 2024 Sep;1867(3):195045. doi: 10.1016/j.bbagrm.2024.195045. Epub 2024 Jun 6.
2
The scaffolding protein JADE1 physically links the acetyltransferase subunit HBO1 with its histone H3-H4 substrate.
J Biol Chem. 2018 Mar 23;293(12):4498-4509. doi: 10.1074/jbc.RA117.000677. Epub 2018 Jan 30.
3
Guiding the HBO1 complex function through the JADE subunit.
Nat Struct Mol Biol. 2024 Jul;31(7):1039-1049. doi: 10.1038/s41594-024-01245-2. Epub 2024 Mar 6.
4
KAT6A chimeras form a self-reinforcing epigenetic module with NURF and MLL/COMPASS to sustain AML.
Genome Biol. 2025 Aug 19;26(1):253. doi: 10.1186/s13059-025-03743-y.
6
Stem cell plasticity, acetylation of H3K14, and de novo gene activation rely on KAT7.
Cell Rep. 2023 Jan 31;42(1):111980. doi: 10.1016/j.celrep.2022.111980. Epub 2023 Jan 14.
7
Targeting chromatin modifying complexes in acute myeloid leukemia.
Stem Cells Transl Med. 2025 Feb 11;14(2). doi: 10.1093/stcltm/szae089.
8
The transcription factor HOXA9 induces expression of the chromatin modifier SMYD3 to drive leukemogenesis.
J Biol Chem. 2025 May 30;301(7):110320. doi: 10.1016/j.jbc.2025.110320.
9
HBO1-MLL interaction promotes AF4/ENL/P-TEFb-mediated leukemogenesis.
Elife. 2021 Aug 25;10:e65872. doi: 10.7554/eLife.65872.
10
Multifunctional acyltransferase HBO1: a key regulatory factor for cellular functions.
Cell Mol Biol Lett. 2024 Nov 14;29(1):141. doi: 10.1186/s11658-024-00661-y.

引用本文的文献

本文引用的文献

1
HBO1 catalyzes lysine lactylation and mediates histone H3K9la to regulate gene transcription.
Nat Commun. 2024 Apr 26;15(1):3561. doi: 10.1038/s41467-024-47900-6.
2
The winged helix domain of MORF binds CpG islands and the TAZ2 domain of p300.
iScience. 2024 Feb 29;27(4):109367. doi: 10.1016/j.isci.2024.109367. eCollection 2024 Apr 19.
3
Genome-wide CRISPR activation screen identifies JADE3 as an antiviral activator of NF-kB-dependent IFITM3 expression.
J Biol Chem. 2024 Apr;300(4):107153. doi: 10.1016/j.jbc.2024.107153. Epub 2024 Mar 9.
4
Guiding the HBO1 complex function through the JADE subunit.
Nat Struct Mol Biol. 2024 Jul;31(7):1039-1049. doi: 10.1038/s41594-024-01245-2. Epub 2024 Mar 6.
5
ING4 and ING5 are essential for histone H3 lysine 14 acetylation and epicardial cell lineage development.
Development. 2024 Mar 1;151(5). doi: 10.1242/dev.202617. Epub 2024 Mar 6.
6
The ORFIUS complex regulates ORC2 localization at replication origins.
NAR Cancer. 2024 Jan 29;6(1):zcae003. doi: 10.1093/narcan/zcae003. eCollection 2024 Mar.
8
JAZF1: A metabolic actor subunit of the NuA4/TIP60 chromatin modifying complex.
Front Cell Dev Biol. 2023 Apr 7;11:1134268. doi: 10.3389/fcell.2023.1134268. eCollection 2023.
9
MOZ/ENL complex is a recruiting factor of leukemic AF10 fusion proteins.
Nat Commun. 2023 Apr 8;14(1):1979. doi: 10.1038/s41467-023-37712-5.
10
MORF and MOZ acetyltransferases target unmethylated CpG islands through the winged helix domain.
Nat Commun. 2023 Feb 8;14(1):697. doi: 10.1038/s41467-023-36368-5.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验