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The trimeric coiled‐coil HSBP1 protein promotes WASH complex assembly at centrosomes

Sai Visweshwaran 1 Peter Thomason 2 Raphaël Guérois 3 Sophie Vacher 4 Evgeny Denisov 5, 6 Lubov Tashireva 7 Maria Lomakina 8 Christine Lazennec‐schurdevin 1 Goran Lakisic 1 Sergio Lilla 2 Nicolas Molinie 1 Véronique Henriot 1 Yves Mechulam 1 Antonina Alexandrova 8 Nadezhda Cherdyntseva 5 Ivan Bièche 9, 4 Emmanuelle Schmitt 1 Robert Insall 2 Alexis Gautreau 1, 10, *
* Corresponding author
1 BIOC - Laboratoire de Biochimie de l'Ecole polytechnique
2 CR-UK Beatson Institute, Institute of Cancer Sciences
3 I2BC - Institut de Biologie Intégrative de la Cellule
4 Service de Génétique - Unité de Pharmacogénomique
5 Laboratory of Molecular Oncology and Immunology - Cancer Institute
6 Laboratory for Translational Cellular and Molecular Biomedicine
7 Department of General and Molecular Pathology
8 Institute of Carcinogenesis
9 Facultés des sciences pharmaceutiques et biologiques
10 MIPT - Moscow Institute of Physics and Technology [Moscow]
Abstract : The Arp2/3 complex generates branched actin networks that exert pushing forces onto different cellular membranes. WASH complexes activate Arp2/3 complexes at the surface of endosomes and thereby fission transport intermediates containing endocytosed receptors, such as α5β1 integrins. How WASH complexes are assembled in the cell is unknown. Here, we identify the small coiled-coil protein HSBP1 as a factor that specifically promotes the assembly of a ternary complex composed of CCDC53, WASH, and FAM21 by dissociating the CCDC53 homotrimeric precursor. HSBP1 operates at the centrosome, which concentrates the building blocks. HSBP1 depletion in human cancer cell lines and in Dictyostelium amoebae phenocopies WASH depletion, suggesting a critical role of the ternary WASH complex for WASH functions. HSBP1 is required for the development of focal adhesions and of cell polarity. These defects impair the migration and invasion of tumor cells. Overexpression of HSBP1 in breast tumors is associated with increased levels of WASH complexes and with poor prognosis for patients.
Keywords : Arp2/3 complex Actin cytoskeleton Cell migration and invasion Centrosome Multiprotein complex assembly
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https://hal-polytechnique.archives-ouvertes.fr/hal-01974215
Contributor : Aurélien Arnoux <>
Submitted on : Tuesday, January 8, 2019 - 4:24:03 PM
Last modification on : Wednesday, November 25, 2020 - 5:06:03 PM

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Sai Visweshwaran, Peter Thomason, Raphaël Guérois, Sophie Vacher, Evgeny Denisov, et al.. The trimeric coiled‐coil HSBP1 protein promotes WASH complex assembly at centrosomes. EMBO Journal, EMBO Press, 2018, 37 (13), pp.e97706. ⟨10.15252/embj.201797706⟩. ⟨hal-01974215⟩

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