Nuclear tension controls mitotic entry by regulating cyclin B1 nuclear translocation

J Cell Biol. 2022 Dec 5;221(12):e202205051. doi: 10.1083/jcb.202205051. Epub 2022 Oct 12.

Abstract

As cells prepare to divide, they must ensure that enough space is available to assemble the mitotic machinery without perturbing tissue homeostasis. To do so, cells undergo a series of biochemical reactions regulated by cyclin B1-CDK1 that trigger cytoskeletal reorganization and ensure the coordination of cytoplasmic and nuclear events. Along with the biochemical events that control mitotic entry, mechanical forces have recently emerged as important players in cell-cycle regulation. However, the exact link between mechanical forces and the biochemical pathways that control mitotic progression remains unknown. Here, we identify a tension-dependent signal on the nucleus that sets the time for nuclear envelope permeabilization (NEP) and mitotic entry. This signal relies on actomyosin contractility, which unfolds the nucleus during the G2-M transition, activating the stretch-sensitive cPLA2 on the nuclear envelope and regulating the nuclear translocation of cyclin B1. Our data demonstrate how nuclear tension during the G2-M transition contributes to timely and efficient mitotic spindle assembly and prevents chromosomal instability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus*
  • Actomyosin / metabolism
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism
  • Cell Nucleus / metabolism
  • Chromosomal Instability
  • Cyclin B1* / genetics
  • Cyclin B1* / metabolism
  • Mitosis*
  • Nuclear Envelope / metabolism
  • Phospholipases A2, Cytosolic / metabolism
  • Spindle Apparatus / metabolism

Substances

  • Cyclin B1
  • Actomyosin
  • CDC2 Protein Kinase
  • Phospholipases A2, Cytosolic