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Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites

Nat Commun. 2019; 
Holdgaard SG, Cianfanelli V, Pupo E, Lambrughi M, Lubas M, Nielsen JC, Eibes S, Maiani E, Harder LM, Wesch N0, Foged MM, Maeda K, Nazio F, de la Ballina LR, Dötsch V0, Brech A, Frankel LB, Jäättelä M, Locatelli F, Barisic M, Andersen JS, Bekker-Jensen S, Lund AH, Rogov VV0, Papaleo E, Lanzetti L, De Zio D, Cecconi F0,
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Peptide Synthesis For ITC experiments, LC3 and GABARAP proteins were obtained based on the protocols described elsewhere75. Human PCM1 LIR-contained peptide (1958-SDEEDFVKVEDLPLKLTIY-1976, core LIR is underlined) was purchased from GenScript Inc (N.J., USA). Before experiments, all proteins and peptide were equilibrated with a buffer containing 50 mM Tris-HCl, pH 7.4, 100 mM NaCl; and supplied with 5 mM protease inhibitors cocktail. Get A Quote

摘要

The centrosome is the master orchestrator of mitotic spindle formation and chromosome segregation in animal cells. Centrosome abnormalities are frequently observed in cancer, but little is known of their origin and about pathways affecting centrosome homeostasis. Here we show that autophagy preserves centrosome organization and stability through selective turnover of centriolar satellite components, a process we termed doryphagy. Autophagy targets the satellite organizer PCM1 by interacting with GABARAPs via a C-terminal LIR motif. Accordingly, autophagy deficiency results in accumulation of large abnormal centriolar satellites and a resultant dysregulation of centrosome composition. These alterations have crit... More

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