Gli1-induced deubiquitinase USP48 aids glioblastoma tumorigenesis by stabilizing Gli1.

ABSTRACT: Aberrant activation of the Hedgehog (Hh) signaling pathway drives the tumorigenesis of multiple cancers. In this study, we screened a panel of deubiquitinases that may regulate the Hh pathway. We find that deubiquitinase USP48 activates Gli-dependent transcription by stabilizing Gli1 protein. Mechanistically, USP48 interacts with Gli1 and cleaves its ubiquitin off directly. In glioblastoma cells, knockdown of USP48 inhibits cell proliferation and the expression of Gli1's downstream targets, which leads to repressed glioblastoma tumorigenesis. Importantly, USP48's effect on cell proliferation and tumorigenesis depends to some extent on Gli1. In addition, we find that the Sonic Hedgehog (SHH) pathway induces USP48 expression through Gli1-mediated transcriptional activation, which forms thus

SUBMITTER: Zhou A 

PROVIDER: S-EPMC5538423 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature