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

Year: 2016

Type: article

Abstract: 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.

Source: Nature Communications

DOI: 10.1038/ncomms13343

Authors: Felicia Gray, Hyo Je Cho, Shirish Shukla, Shihan He, Ashley Harris, Bohdan Boytsov, Łukasz Jaremko, Mariusz Jaremko, Borries Demeler, Elizabeth R. Lawlor, Jolanta Grembecka, Tomasz Cierpicki

Institutions: University of Michigan, German Center for Neurodegenerative Diseases, Max Planck Institute for Biophysical Chemistry, The University of Texas at San Antonio Health Science Center

Language: English

Topic: Epigenetics and DNA Methylation

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $6,990

Funders: U.S. Department of Energy, Michigan Economic Development Corporation, Leukemia and Lymphoma Society, National Institutes of Health, Office of Science, Michigan Technology Tri-Corridor, National Cancer Institute, National Institute of General Medical Sciences, Basic Energy Sciences

OpenAlex ID: W2554647387