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The mechanoresponsive chromosomal passenger complex sustains furrow ingression under confinement
Chenxin Wang1 , Jingjing Ding1 , Chao Wang1,2 , Maiyong Zhang1 , Junjie Wu1 , Bowen Chen1 , Hui Yang1 , Ting Gang Chew1,2,3,4,*
1The Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Haining 314400, China
2Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China
3College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh EH4 2XR, UK
4State Key Laboratory of Biobased Transportation Fuel Technology, Zhejiang University, Hangzhou 310027, China
Collection on Cytoskeleton Research: from Structure to Function
*Correspondence to:Ting Gang Chew , Email:tinggang80@gmail.com
J Mol Cell Biol, Volume 17, Issue 4, April 2025, mjaf019,  https://doi.org/10.1093/jmcb/mjaf019
Keyword: cytokinesis, mitosis, confinement, mechanobiology

Cells sense and respond to forces from neighbouring cells and the extracellular matrix during growth and division. When cells undergo mitosis in a confined environment like in the tumour environment, high compressive stress causes unstable cell cortex and prolonged mitosis. Confined mitotic cells frequently experience chromosome loss and multipolar division. How the cortical instability affects cytokinesis under confinement is unclear. Here, we show that confined mitotic cells undergo furrow ingression comparable to unconfined mitotic cells but are strongly reliant on Aurora B kinase, a catalytic subunit of the chromosomal passenger complex (CPC) for its completion. Mechanistically, the cortical pool of CPC via the scaffolding protein INCENP sustains Aurora B at the equatorial cortex to drive furrow ingression under confinement. We identified mechanoresponsive elements within the single alpha-helix domain of INCENP that maintain the cortical CPC at the equatorial cortex to promote furrow ingression in response to high compressive stress. Thus, the cortical INCENP not only binds to actin filaments but also mechanically responds to forces at the equatorial cortex to regulate the CPC during confined cytokinesis.