BAG3 regulates cilia homeostasis of glioblastoma via its WW domain

Building on our previously identified and novel deciliating function of BAG3, we further decipher the molecular mechanisms of BAG3-regulated cilia homeostasis in glioblastoma (GBM). Based on identification of BAG3 interactomes and the contribution of different functional domains we now demonstrate that BAG3 regulates cilia homeostasis via its WW domain and modulation of YAP1 activity/downstream YAP1-dependent signaling. We also provide evidence for a complex interaction network of BAG3 with several pathways regulating cilia homeostasis at the level of ciliogenesis and cilium degradation. AbstractThe 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 adheren t 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 res...
Source: BioFactors - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research