title: Aurora kinase-induced phosphorylation excludes transcription factor RUNX from the chromatin to facilitate proper mitotic progression.
abstract: 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.
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599;
authors.forename: Linda Shyue Huey
authors.initials: LS
authors.lastname: Chuang
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599;
authors.forename: Jian Ming
authors.initials: JM
authors.lastname: Khor
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore 637551;
authors.forename: Soak Kuan
authors.initials: SK
authors.lastname: Lai
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599;
authors.forename: Shubham
authors.initials: S
authors.lastname: Garg
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599;
authors.forename: Vaidehi
authors.initials: V
authors.lastname: Krishnan
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore 637551;
authors.forename: Cheng-Gee
authors.initials: CG
authors.lastname: Koh
authors.affiliation: Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore 169857.
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599; csiitoy@nus.edu.sg.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ito
mesh_terms: D000818:Animals; D064127:Aurora Kinases / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D002843:Chromatin / Q000378:metabolism; D050677:Core Binding Factor Alpha 3 Subunit / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050657:Core Binding Factor alpha Subunits / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D009154:Mutation; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013912:Threonine / Q000737:chemistry
chemical_list: D002843:Chromatin; D050677:Core Binding Factor Alpha 3 Subunit; D050657:Core Binding Factor alpha Subunits; D011994:Recombinant Proteins; C493729:Runx3 protein, human; D013912:Threonine; D004247:DNA; D064127:Aurora Kinases
keywords: Aurora kinase; RUNX; centrosome; mitosis; phosphorylation