10.6084/m9.figshare.1246748.v2
Miyoung Lee
Miyoung
Lee
Ashok R Venkitaraman
Ashok
R Venkitaraman
A cancer-associated mutation inactivates a region of the high-mobility group protein HMG20b essential for cytokinesis
Taylor & Francis Group
2015
HMG 20b
HMG 20b cells
HMG 20b impairing cytokinesis
HMG 20b mutations
controls mitotic cell division
engendering chromosome instability
HMG 20b residue Ala 247
tumor suppressor mechanisms
region
brca
2015-10-09 14:54:20
Journal contribution
https://tandf.figshare.com/articles/journal_contribution/A_cancer_associated_mutation_inactivates_a_region_of_the_high_mobility_group_protein_HMG20b_essential_for_cytokinesis/1246748
<div><p>Defects in the completion of cell division by cytokinesis have long been proposed to foster carcinogenesis by engendering chromosome instability, but few tumor suppressor mechanisms controlling this process have so far been identified. Here, we identify a carboxyl (C)-terminal region of the high-mobility group protein HMG20b that is essential for cytokinesis, and report that it is inactivated by a cancer-associated mutation. We find that a C-terminal region of HMG20b spanning residues 173–317 is necessary and sufficient not only for its localization to cytokinetic structures, but also for its interaction with the tumor suppressor BRCA2, implicated in the abscission step of cytokinesis. Indeed, expression of this C-terminal HMG20b region suffices to restore cytokinesis in HMG20b-depleted cells. The non-conservative substitution of HMG20b residue Ala247 with Pro, reported in human lung cancer, disrupts these activities of HMG20b, impairing cytokinesis in a <i>trans</i>-dominant manner. Our findings provide fresh insight into the mechanism by which the HMG20b-BRCA2 complex controls mitotic cell division, and implicate heterozygous HMG20b mutations affecting cytokinesis regulation in the genesis of human cancers.</p></div>