Nuclear tension controls mitotic entry by regulating cyclin B1 nuclear translocation

Autores da FMUP

• Andreia Cristina Matos Oliveira

  Autor

• Hélder José Martins Maiato

  Autor

• João Pedro Melo Marques Pinho Ferreira

  Autor

Participantes de fora da FMUP

• Dantas, M
• Aguiar, P.

Unidades de investigação

• Biomedicina

• Ciências da Saúde Pública e Forenses, e Educação Médica

• Cirurgia e Fisiologia

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Mitotic entry is regulated by the activity of cyclin B1-CDK1 complexes. In this study, Dantas et al. show that actomyosin-dependent nuclear tension during prophase regulates cyclin B1 nuclear translocation and has implications for chromosome segregation efficiency. 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.

Keywords

• CELL-CYCLE; PHOSPHORYLATION; ACTIVATION; LOCALIZATION; MITOSIS; IMPORT; KINASE; PROGRESSION; CHECKPOINT; COMPLEXES