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BAG3 regulates cilia homeostasis of glioblastoma via its WW domain

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 stemness, identified interactors in sphere-cultured cells included different stem cell markers (SOX2, OLIG2, NES), while interactomes of adherent BAG3-proficient cells indicated a shift towards involvement of BAG3 in regulation of cilium assembly (ACTR3, 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Glioblastoma

SUBMITTER: Thorsten Mosler

LAB HEAD: Donat Kögel

PROVIDER: PXD050279 | Pride | 2024-04-09

REPOSITORIES: Pride

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