ArticleCell death and differentiation2022
The phosphorylation and dephosphorylation switch of VCP/p97 regulates the architecture of centrosome and spindle.
Article in Cell death and differentiation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- p97 Inhibition Synergistically Enhances Hypomethylating Therapy through Targeting of PLK1 in Acute Myeloid Leukemia.Cancer research communications · 2026Article
- Inhibition of PGK1 enhances sensitivity to tyrosine kinase inhibitor in T315I-mutant leukemia.Acta pharmaceutica Sinica. B · 2026Article
- Kinesin Spindle Protein (KIF11) in Mitosis and Cancer.International journal of molecular sciences · 2025Review
- Harnessing p97/VCP: A Transformative AAA+ ATPase Target for Next-Generation Cancer Therapeutics.Cancers · 2025Review
- The nuclear exosome co-factor MTR4 shapes the transcriptome for meiotic initiation.Nature communications · 2025Article
- The protein segregase VCP/p97 promotes host antifungal defense via regulation of SYK activation.PLoS pathogens · 2024Article
- An autosomal-dominant childhood-onset disorder associated with pathogenic variants in VCP.American journal of human genetics · 2023Article
- DUSP1 interacts with and dephosphorylates VCP to improve mitochondrial quality control against endotoxemia-induced myocardial dysfunction.Cellular and molecular life sciences : CMLS · 2023Article
- EMC3 regulates mesenchymal cell survival via control of the mitotic spindle assembly.iScience · 2023Article
- Molecular subtypes based on centrosome-related genes can predict prognosis and therapeutic responsiveness in patients with low-grade gliomas.Frontiers in oncology · 2023Article
- The functional importance of VCP to maintaining cellular protein homeostasis.Biochemical Society transactions · 2022Review
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proper orientation of centrosome and spindle is essential for genome stability; however, the mechanism that governs these processes remains elusive. Here, we demonstrated that polo-like kinase 1 (Plk1), a key mitotic kinase, phosphorylates residue Thr76 in VCP/p97 (an AAA-ATPase), at the centrosome from prophase to anaphase. This phosphorylation process recruits VCP to the centrosome and in this way, it regulates centrosome orientation. VCP exhibits strong co-localization with Eg5 (a mitotic kinesin motor), at the mitotic spindle, and the dephosphorylation of Thr76 in VCP is required for the enrichment of both VCP and Eg5 at the spindle, thus ensuring proper spindle architecture and chromosome segregation. We also showed that the phosphatase, PTEN, is responsible for the dephosphorylation of Thr76 in VCP; when PTEN was knocked down, the normal spread of VCP from the centrosome to the spindle was abolished. Cryo-EM structures of VCP
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