BMI1 regulates PRC1 architecture and activity through homo- and hetero-oligomerization

被引：53

作者：

Gray, Felicia ^{[1
]}

Cho, Hyo Je ^{[1
]}

Shukla, Shirish ^{[1
]}

He, Shihan ^{[1
]}

Harris, Ashley ^{[2
,3
]}

Boytsov, Bohdan ^{[1
]}

Jaremko, Lukasz ^{[4
,5
]}

Jaremko, Mariusz ^{[5
]}

Demeler, Borries ^{[6
]}

Lawlor, Elizabeth R. ^{[1
,2
,3
]}

Grembecka, Jolanta ^{[1
]}

Cierpicki, Tomasz ^{[1
]}

机构：

[1] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Translat Oncol Program, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA

[4] DZNE, Fassberg 11, D-37077 Gottingen, Germany

[5] Max Planck Inst Biophys Chem, NMR Based Dept Struct Biol, Fassberg 11, D-37077 Gottingen, Germany

[6] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

关键词：

X-RAY; MOLECULAR MARKER; H2A UBIQUITYLATION; PROTEIN BMI-1; POLYCOMB; COMPLEX; GENE; NMR; REFINEMENT; IDENTIFICATION;

D O I：

10.1038/ncomms13343

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 beta-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.

引用

页数：12

共 70 条

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