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Cell Discov. 2016 Oct 4;2:16033. eCollection 2016.

ASK1 controls spindle orientation and positioning by phosphorylating EB1 and stabilizing astral microtubules.

Author information

1
Institute of Biomedical Sciences, College of Life Sciences, Key Laboratory of Animal Resistance Biology of Shandong Province, Key Laboratory of Molecular and Nano Probes of the Ministry of Education, Shandong Normal University, Jinan, China; State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Protein Science of Tianjin, Key Laboratory of Bioactive Materials of the Ministry of Education, Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China.
2
Institute of Biomedical Sciences, College of Life Sciences, Key Laboratory of Animal Resistance Biology of Shandong Province, Key Laboratory of Molecular and Nano Probes of the Ministry of Education, Shandong Normal University , Jinan, China.
3
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Protein Science of Tianjin, Key Laboratory of Bioactive Materials of the Ministry of Education, Department of Genetics and Cell Biology, College of Life Sciences, Nankai University , Tianjin, China.

Abstract

Orientation and positioning of the mitotic spindle are involved in dictating cell division axis and cleavage site, and play important roles in cell fate determination and tissue morphogenesis. However, how spindle movement is controlled to achieve a defined alignment within the dividing cell is not fully understood. Here, we describe an unexpected role for apoptosis signal-regulating kinase 1 (ASK1) in regulating spindle behavior. We find that ASK1 is required for proper mitotic progression and daughter cell adhesion to the substratum. ASK1 interacts with end-binding protein 1 (EB1) and phosphorylates EB1 at serine 40, threonine 154 and threonine 206, enhancing its binding to the plus ends of astral microtubules. Consequently, astral microtubules are stabilized and therefore capable of mediating spindle interaction with the cell cortex, a requirement for spindle movement. These findings reveal a previously undiscovered function of ASK1 in cell division by regulating spindle orientation and positioning, and point to the importance of protein phosphorylation in the regulation of spindle behavior.

KEYWORDS:

apoptosis signal-regulating kinase 1; astral microtubule; end-binding protein 1; phosphorylation; spindle orientation; spindle positioning

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