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  CDK1-cyclin-B1-induced kindlin degradation drives focal adhesion disassembly at mitotic entry

Chen, N.-P., Aretz, J., & Fässler, R. (2022). CDK1-cyclin-B1-induced kindlin degradation drives focal adhesion disassembly at mitotic entry. Nature Cell Biology. doi:10.1038/s41556-022-00886-z.

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Chen, Nan-Peng1, Author              
Aretz, Jonas1, Author              
Fässler, Reinhard1, Author              
Affiliations:
1Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

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Free keywords: DNA-DAMAGE RESPONSE; INTEGRIN ACTIVATION; UBIQUITIN LIGASE; QUANTITATIVE PROTEOMICS; CELL-SHAPE; PHOSPHORYLATION; PAXILLIN; TALIN; ACTIN; RECRUITMENTCell Biology;
 Abstract: The disassembly of integrin-containing focal adhesions (FAs) at mitotic entry is essential for cell rounding, mitotic retraction fibre formation, bipolar spindle positioning and chromosome segregation. The mechanism that drives FA disassembly at mitotic entry is unknown. Here, we show that the CDK1-cyclin B1 complex phosphorylates the integrin activator kindlin, which results in the recruitment of the cullin 9-FBXL10 ubiquitin ligase complex that mediates kindlin ubiquitination and degradation. This molecular pathway is essential for FA disassembly and cell rounding, as phospho-inhibitory mutations of the CDK1 motif prevent kindlin degradation, FA disassembly and mitotic cell rounding. Conversely, phospho-mimetic mutations promote kindlin degradation in interphase, accelerate mitotic cell rounding and impair mitotic retraction fibre formation. Despite the opposing effects on kindlin stability, both types of mutations cause severe mitotic spindle defects, apoptosis and aneuploidy. Thus, the exquisite regulation of kindlin levels at mitotic entry is essential for cells to progress accurately through mitosis. Chen et al. report that at mitotic entry, cyclin B1-CDK1 phosphorylates the focal adhesion protein kindlin to induce its proteasomal degradation and promote focal adhesion disassembly and mitotic rounding.

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Language(s): eng - English
 Dates: 2022
 Publication Status: Published online
 Pages: 32
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: Nature Cell Biology
  Other : 'Nat. Cell Biol.'
Source Genre: Journal
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Publ. Info: London : Springer Nature
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: - Identifier: ISSN: 1465-7392
CoNE: https://pure.mpg.de/cone/journals/resource/954925625310