BMI1 regulates PRC1 architecture and activity through homo- and hetero-oligomerization.
BMI1 regulates PRC1 architecture and activity through homo- and hetero-oligomerization.
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DOI：
10.1038/ncomms13343
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发表时间：
2016-11-09
影响因子：
16.6
通讯作者：
Cierpicki, Tomasz
中科院分区：
文献类型：
--
作者：
Gray, Felicia;Cho, Hyo Je;Shukla, Shirish;He, Shihan;Harris, Ashley;Boytsov, Bohdan;Jaremko, Lukasz;Jaremko, Mariusz;Demeler, Borries;Lawlor, Elizabeth R.;Grembecka, Jolanta;Cierpicki, Tomasz
BMI1是多梳抑制复合体1(PRC1)的核心成分，新出现的数据支持BMI1在癌症中的作用。BMI1的中心结构域参与蛋白质之间的相互作用，是其致癌活性所必需的。在这里，我们给出了BMI1与多同源蛋白PHc2结合的结构，说明BMI1的中心结构域采用泛素样折叠，并以β-发夹构象结合PHc2。出乎意料的是，我们发现UBL域参与了BMI1的同源齐聚。我们证明，BMI1与多同源蛋白的相互作用和通过UBL域的同源齐聚对于PRC1的H_2A泛素化活性和U2OS细胞的克隆形成能力都是必要的。在这里，我们还强调需要联合应用核磁共振光谱和X射线结晶学来确定BMI1-PHC2络合物的整体结构。BMI1是多梳抑制复合体1的核心元件，被认为在多种癌症中具有致癌活性。在这里，作者报道了BMI1与PHC2蛋白结合的结构，鉴定了BMI1同源齐聚界面，并分析了BMI1蛋白-蛋白质相互作用在PRC1功能中的作用。
BMI1 is a core component of the polycomb repressive complex 1 (PRC1) and emerging data support a role of BMI1 in cancer. The central domain of BMI1 is involved in protein–protein interactions and is essential for its oncogenic activity. Here, we present the structure of BMI1 bound to the polyhomeotic protein PHC2 illustrating that the central domain of BMI1 adopts an ubiquitin-like (UBL) fold and binds PHC2 in a β-hairpin conformation. Unexpectedly, we find that the UBL domain is involved in homo-oligomerization of BMI1. We demonstrate that both the interaction of BMI1 with polyhomeotic proteins and homo-oligomerization via UBL domain are necessary for H2A ubiquitination activity of PRC1 and for clonogenic potential of U2OS cells. Here, we also emphasize need for joint application of NMR spectroscopy and X-ray crystallography to determine the overall structure of the BMI1–PHC2 complex. BMI1, a core element of the polycomb repressive complex 1, is suggested to have oncogenic activity in a variety of cancers. Here, the authors report the structure of BMI1 bound to the protein PHC2, identify BMI1 homo-oligomerization interfaces, and analyse the role of BMI1 protein-protein interactions in PRC1 function.
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影响因子：
11.5
作者：
Cooper, Aaron;van Doorninck, John;Lawlor, Elizabeth R.
通讯作者：
Lawlor, Elizabeth R.
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
2.4
作者：
Demeler, Borries;Brookes, Emre
通讯作者：
Brookes, Emre
影响因子：
2.7
作者：
DELAGLIO, F;GRZESIEK, S;BAX, A
通讯作者：
BAX, A
影响因子：
2.9
作者：
Barycki, JJ;O'Brien, LK;Banaszak, LJ
通讯作者：
Banaszak, LJ