SALL4 is a CRL3^REN/KCTD11 substrate that drives Sonic Hedgehog-dependent medulloblastoma.

ABSTRACT: The Sonic Hedgehog (SHH) pathway is crucial regulator of embryonic development and stemness. Its alteration leads to medulloblastoma (MB), the most common malignant pediatric brain tumor. The SHH-MB subgroup is the best genetically characterized, however the molecular mechanisms responsible for its pathogenesis are not fully understood and therapeutic benefits are still limited. Here, we show that the pro-oncogenic stemness regulator Spalt-like transcriptional factor 4 (SALL4) is re-expressed in mouse SHH-MB models, and its high levels correlate with worse overall survival in SHH-MB patients. Proteomic analysis revealed that SALL4 interacts with REN/KCTD11 (here REN), a substrate receptor subunit of the Cullin3-RING ubiquitin ligase complex (CRL3^REN) and a tumor suppressor lost

SUBMITTER: Lospinoso Severini L 

PROVIDER: S-EPMC10850099 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature