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

作者：Chuang Linda Shyue Huey; Khor Jian Ming; Lai Soak Kuan; Garg Shubham; Krishnan Vaidehi; Koh Cheng Gee; Lee Sang Hyun; Ito Yoshiaki^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2016, 113(23): 6490-6495.

DOI：10.1073/pnas.1523157113

• RUNX
• phosphorylation
• mitosis
• centrosome
• Aurora kinase

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 formitotic 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.

• 出版日期2016-6-7
• 单位南阳理工学院