Aurora kinase-induced phosphorylation excludes transcription factor RUNX from the chromatin to facilitate proper mitotic progression

Aurora kinase-induced phosphorylation excludes transcription factor RUNX from the chromatin to facilitate proper mitotic progression

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, w...

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Bibliographic Details
Main Authors: Chuang, Linda Shyue Huey, Khor, Jian Ming, Lai, Soak Kuan, Garg, Shubham, Krishnan, Vaidehi, Koh, Cheng-Gee, Lee, Sang Hyun, Ito, Yoshiaki
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2017
Subjects:
RUNX
Phosphorylation
Online Access:https://hdl.handle.net/10356/85151
http://hdl.handle.net/10220/43655
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Institution: Nanyang Technological University
Language: English
Description
Summary: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.

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