2. Academic Validation
  3. BAG3 regulates cilia homeostasis of glioblastoma via its WW domain

BAG3 regulates cilia homeostasis of glioblastoma via its WW domain

  • Biofactors. 2024 Apr 24. doi: 10.1002/biof.2060.
Caterina Roth 1,  Lara Paulini 1,  Marina E Hoffmann 2,  Thorsten Mosler 2,  Ivan Dikic 2 3,  Andreas Brunschweiger 4,  Hagen Körschgen 5,  Christian Behl 5,  Benedikt Linder 1,  Donat Kögel 1 6 7
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Experimental Neurosurgery, University Hospital, Goethe University, Frankfurt am Main, Germany.
  • 2 Institute of Biochemistry II, Goethe University, Frankfurt am Main, Germany.
  • 3 Buchmann Institute for Molecular Life Sciences, Goethe University, Frankfurt am Main, Germany.
  • 4 Institute of Pharmacy and Food Chemistry, Faculty of Chemistry and Pharmacy, Julius-Maximilians-Universität, Würzburg, Germany.
  • 5 Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
  • 6 German Cancer Consortium (DKTK), Partner Site Frankfurt, Frankfurt am Main, Germany.
  • 7 German Cancer Research Center DKFZ, Heidelberg, Germany.
PMID: 38655699 DOI: 10.1002/biof.2060
Abstract

The multidomain protein BAG3 exerts pleiotropic oncogenic functions in many tumor entities including glioblastoma (GBM). Here, we compared BAG3 protein-protein interactions in either adherently cultured or stem-like cultured U251 GBM cells. In line with BAG3's putative role in regulating stem-like properties, identified interactors in sphere-cultured cells included different stem cell markers (SOX2, OLIG2, and NES), while interactomes of adherent BAG3-proficient cells indicated a shift toward involvement of BAG3 in regulation of cilium assembly (ACTR3 and ARL3). Applying a set of BAG3 deletion constructs we could demonstrate that none of the domains except the WW domain are required for suppression of cilia formation by full-length BAG3 in U251 and U343 cells. In line with the established regulation of the Hippo pathway by this domain, we could show that the WW mutant fails to rescue YAP1 nuclear translocation. BAG3 depletion reduced activation of a YAP1/AURKA signaling pathway and induction of PLK1. Collectively, our findings point to a complex interaction network of BAG3 with several pathways regulating cilia homeostasis, involving processes related to ciliogenesis and cilium degradation.

Keywords

BAG3; WW domain; YAP1; YAP1 signaling; cilia homeostasis; glioblastoma; primary cilia; stemness.

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