ArticleOncogene2022
Mitotic phosphorylation of tumor suppressor DAB2IP maintains spindle assembly checkpoint and chromosomal stability through activating PLK1-Mps1 signal pathway and stabilizing mitotic checkpoint complex.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 16 citations in OpenAlex.
- LIPT1 loss confers replication stress and PARP inhibitor sensitivity through PrimPol-mediated ssDNA gaps.Science advances · 2026Article
- [Protein Expression Levels of the DCAF4-MEN1-hTERT Axis in Patients With Colon Adenocarcinoma and Their Relationship With Clinicopathological Characteristics and Prognosis].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026Article
- DAB2IP: unifying cardiovascular pathogenesis and cardiovascular brain crosstalk.Frontiers in cardiovascular medicine · 2026Review
- Nuclear DAB2IP regulates DNA replication initiation through activating PLK1-mediated HBO1 phosphorylation.Nucleic acids research · 2025Article
- EPSD 2.0: An Updated Database of Protein Phosphorylation Sites Across Eukaryotic Species.Genomics, proteomics & bioinformatics · 2025Article
- Lipoylation inhibition enhances radiation control of lung cancer by suppressing homologous recombination DNA damage repair.Science advances · 2025Article
- An update on the tumor-suppressive functions of the RasGAP protein DAB2IP with focus on therapeutic implications.Cell death and differentiation · 2024Review
- Cancer testis antigens: Emerging therapeutic targets leveraging genomic instability in cancer.Molecular therapy. Oncology · 2024Review
- PLK1 and FoxM1 expressions positively correlate in papillary thyroid carcinoma and their combined inhibition results in synergistic anti-tumor effects.Molecular oncology · 2024Article
- Gene expression ranking change based single sample pre-disease state detection.Frontiers in genetics · 2024Article
- Maintaining Genome Integrity: Protein Kinases and Phosphatases Orchestrate the Balancing Act of DNA Double-Strand Breaks Repair in Cancer.International journal of molecular sciences · 2023Review
- Hippo signaling and histone methylation control cardiomyocyte cell cycle re-entry through distinct transcriptional pathways.PloS one · 2023Article
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10 authors at 5 institutions in 3 countries.
Funding
Abstract
Chromosomal instability (CIN) is a driving force for cancer development. The most common causes of CIN include the dysregulation of the spindle assembly checkpoint (SAC), which is a surveillance mechanism that prevents premature chromosome separation during mitosis by targeting anaphase-promoting complex/cyclosome (APC/C). DAB2IP is frequently silenced in advanced prostate cancer (PCa) and is associated with aggressive phenotypes of PCa. Our previous study showed that DAB2IP activates PLK1 and functions in mitotic regulation. Here, we report the novel mitotic phosphorylation of DAB2IP by Cdks, which mediates DAB2IP's interaction with PLK1 and the activation of the PLK1-Mps1 pathway. DAB2IP interacts with Cdc20 in a phosphorylation-independent manner. However, the phosphorylation of DAB2IP inhibits the ubiquitylation of Cdc20 in response to SAC, and blocks the premature release of the APC/C-MCC. The PLK1-Mps1 pathway plays an important role in mitotic checkpoint complex (MCC) assembly. It is likely that DAB2IP acts as a scaffold to aid PLK1-Mps1 in targeting Cdc20. Depletion or loss of the Cdks-mediated phosphorylation of DAB2IP destabilizes the MCC, impairs the SAC, and increases chromosome missegregation and subsequent CIN, thus contributing to tumorigenesis. Collectively, these results demonstrate the mechanism of DAB2IP in SAC regulation and provide a rationale for targeting the SAC to cause lethal CIN against DAB2IP-deficient aggressive PCa, which exhibits a weak SAC.
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