Myst2/Kat7 histone acetyltransferase interaction proteomics reveals tumour-suppressor Niam as a novel binding partner in embryonic stem cells.

Myst2/Kat7 histone acetyltransferase interaction proteomics reveals tumour-suppressor Niam as a novel binding partner in embryonic stem cells.
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DOI:
10.1038/s41598-017-08456-2
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发表时间:
2017-08-15
期刊:
影响因子:
4.6
通讯作者:
Choudhary JS
Choudhary JS
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Pardo M;Yu L;Shen S;Tate P;Bode D;Letney BL;Quelle DE;Skarnes W;Choudhary JS

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MYST组蛋白乙酰转移酶在转录、复制和DNA修复中具有重要功能,因此与发育和癌症有关。在这里,我们通过亲和纯化和质谱联用来表征小鼠胚胎干细胞中Myst2/Kat7/Hbo1蛋白的相互作用。本研究证实,在胚胎干细胞中,Myst2是H3和H4组蛋白乙酰化复合物的一部分,与体细胞中描述的相似。我们发现了一种新的myst2相关蛋白,即肿瘤抑制蛋白Niam (ARF和Mdm2的核相互作用因子)。人类NIAM参与体细胞的染色体分离、p53调控和细胞增殖,但其在胚胎干细胞中的作用尚不清楚。我们描述了第一个Niam胚胎干细胞相互作用组,其中包括在DNA复制和修复,转录,剪接和核糖体生物发生中发挥作用的蛋白质。许多Myst2和Niam结合伙伴是正确胚胎发育所必需的,这意味着Myst2和Niam参与了这一过程的合作调节,并提示Niam在胚胎生物学中的新作用。这些数据为探索Myst2和Niam的基本细胞功能提供了有用的资源,并有助于更深入地了解生物体的早期发育和生存以及癌症。数据可通过ProteomeXchange获得,标识符为PXD005987。
MYST histone acetyltransferases have crucial functions in transcription, replication and DNA repair and are hence implicated in development and cancer. Here we characterise Myst2/Kat7/Hbo1 protein interactions in mouse embryonic stem cells by affinity purification coupled to mass spectrometry. This study confirms that in embryonic stem cells Myst2 is part of H3 and H4 histone acetylation complexes similar to those described in somatic cells. We identify a novel Myst2-associated protein, the tumour suppressor protein Niam (Nuclear Interactor of ARF and Mdm2). Human NIAM is involved in chromosome segregation, p53 regulation and cell proliferation in somatic cells, but its role in embryonic stem cells is unknown. We describe the first Niam embryonic stem cell interactome, which includes proteins with roles in DNA replication and repair, transcription, splicing and ribosome biogenesis. Many of Myst2 and Niam binding partners are required for correct embryonic development, implicating Myst2 and Niam in the cooperative regulation of this process and suggesting a novel role for Niam in embryonic biology. The data provides a useful resource for exploring Myst2 and Niam essential cellular functions and should contribute to deeper understanding of organism early development and survival as well as cancer. Data are available via ProteomeXchange with identifier PXD005987.
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