Aurora kinase-induced phosphorylation excludes transcription factor RUNX from the chromatin to facilitate proper mitotic progression
Chuang, Linda Shyue Huey
Khor, Jian Ming
Lai, Soak Kuan
Lee, Sang Hyun
Date of Issue2016
School of Biological Sciences
The Runt-related transcription factors (RUNX) are master regulators of development and major players in tumorigenesis. Interestingly, unlike most transcription factors, RUNX proteins are detected on the mitotic chromatin and apparatus, suggesting that they are functionally active in mitosis. Here, we identify key sites of RUNX phosphorylation in mitosis. We show that the phosphorylation of threonine 173 (T173) residue within the Runt domain of RUNX3 disrupts RUNX DNA binding activity during mitotic entry to facilitate the recruitment of RUNX proteins to mitotic structures. Moreover, knockdown of RUNX3 delays mitotic entry. RUNX3 phosphorylation is therefore a regulatory mechanism for mitotic entry. Cancer-associated mutations of RUNX3 T173 and its equivalent in RUNX1 further corroborate the role of RUNX phosphorylation in regulating proper mitotic progression and genomic integrity.
Proceedings of the National Academy of Sciences of the United States of America
© 2016 The Author(s) (published by National Academy of Sciences). This is the author created version of a work that has been peer reviewed and accepted for publication in Proceedings of the National Academy of Sciences of the United States of America, published by National Academy of Sciences on behalf of the author(s). It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1073/pnas.1523157113].