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Aurora Kinase-Induced Phosphorylation Excludes Transcription Factor RUNX From the Chromatin to Facilitate Proper Mitotic Progression. (PNAS, May 2016)

Chuang LS1, Khor JM1, Lai SK2, Garg S1, Krishnan V1, Koh CG2, Lee SH3, Ito Y4.

1 Cancer Science Institute of Singapore, National University of Singapore
2 School of Biological Sciences, Nanyang Technological University
3 Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School
4 Cancer Science Institute of Singapore, National University of Singapore

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.

KEYWORDS:
Aurora kinase; RUNX; centrosome; mitosis; phosphorylation

PMID: 27217562