ArticleMolecular biology of the cell2018
Asterless is a Polo-like kinase 4 substrate that both activates and inhibits kinase activity depending on its phosphorylation state.
Article in Molecular biology of the cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 27 citations in OpenAlex.
- Unraveling the molecular details of centriole elongation.Trends open · 2026Article
- Distinct pathophysiological mechanisms of CEP152 variants in microcephaly and brain abnormalities.EMBO molecular medicine · 2026Article
- The Centriole Biogenesis Cycle: Temporal Mechanisms, Autonomy and Coupling to the Cell Cycle and Other Cellular Clocks.Advances in experimental medicine and biology · 2026Review
- Review
- PLK4: Master Regulator of Centriole Duplication and Its Therapeutic Potential.Cytoskeleton (Hoboken, N.J.) · 2025Review
- Binding of CEP152 to PLK4 stimulates kinase activity to promote centriole assembly.Molecular biology of the cell · 2025Article
- Generating CRISPR-edited clonal lines of culturedBiology methods & protocols · 2024Article
- CCDC15 localizes to the centriole inner scaffold and controls centriole length and integrity.The Journal of cell biology · 2023Article
- A simple Turing reaction-diffusion model explains how PLK4 breaks symmetry during centriole duplication and assembly.PLoS biology · 2023Article
- Cep104 is a component of the centriole distal tip complex that regulates centriole growth and contributes to Drosophila spermiogenesis.Current biology : CB · 2023Article
- The E3 ligase Poe promotes Pericentrin degradation.Molecular biology of the cell · 2023Article
- Polo-like kinase 4 homodimerization and condensate formation regulate its own protein levels but are not required for centriole assembly.Molecular biology of the cell · 2023Article
- Balancing the scales: fine-tuning Polo-like kinase 4 to ensure proper centriole duplication.Genes & development · 2022Review
- Autonomous clocks that regulate organelle biogenesis, cytoskeletal organization, and intracellular dynamics.eLife · 2021Review
- Plk4 triggers autonomous de novo centriole biogenesis and maturation.The Journal of cell biology · 2021Article
- A self-assembled cylindrical platform for Plk4-induced centriole biogenesis.Open biology · 2020Review
- Article
- Article
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8 authors at 3 institutions in 1 country.
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Abstract
Centriole assembly initiates when Polo-like kinase 4 (Plk4) interacts with a centriole "targeting-factor." In Drosophila, Asterless/Asl (Cep152 in humans) fulfills the targeting role. Interestingly, Asl also regulates Plk4 levels. The N-terminus of Asl (Asl-A; amino acids 1-374) binds Plk4 and promotes Plk4 self-destruction, although it is unclear how this is achieved. Moreover, Plk4 phosphorylates the Cep152 N-terminus, but the functional consequence is unknown. Here, we show that Plk4 phosphorylates Asl and mapped 13 phospho-residues in Asl-A. Nonphosphorylatable alanine (13A) and phosphomimetic (13PM) mutants did not alter Asl function, presumably because of the dominant role of the Asl C-terminus in Plk4 stabilization and centriolar targeting. To address how Asl-A phosphorylation specifically affects Plk4 regulation, we generated Asl-A fragment phospho-mutants and expressed them in cultured Drosophila cells. Asl-A-13A stimulated kinase activity by relieving Plk4 autoinhibition. In contrast, Asl-A-13PM inhibited Plk4 activity by a novel mechanism involving autophosphorylation of Plk4's kinase domain. Thus, Asl-A's phosphorylation state determines which of Asl-A's two opposing effects are exerted on Plk4. Initially, nonphosphorylated Asl binds Plk4 and stimulates its kinase activity, but after Asl is phosphorylated, a negative-feedback mechanism suppresses Plk4 activity. This dual regulatory effect by Asl-A may limit Plk4 to bursts of activity that modulate centriole duplication.
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