Neuronal Regulator Research Offers Cancer Clues
Inhibiting β-TRCP may help restore REST function in suppressing some tumors in humans
MONDAY, March 24 (HealthDay News) -- The RE1-silencing transcription factor (REST) -- a repressor of neuronal gene expression in non-neuronal lineages and a tumor suppressor in epithelial tissues -- is controlled by an Skp1-Cul1-F-box protein complex containing the F-box protein β-TRCP (SCFβ-TRCP), according to research published in the March 20 issue of Nature.
Thomas F. Westbrook, Ph.D., of the Harvard Partners Center for Genetics and Genomics in Cambridge, Mass., and colleagues write that SCF β-TRCP appears to control REST via ubiquitin-mediated destabilization.
REST can function as both an oncogene and tumor suppressor, depending on the developmental lineages, the authors write. It can inhibit terminal differentiation of neurons, but it may also promote proliferation in the neuronal lineage when it's overproduced or isn't appropriately stabilized. Supporting this idea, REST is overexpressed in medulloblastoma.
"β-TRCP is overexpressed and oncogenic in epithelial cancers, and we identified REST as a key target in this context. This suggests that pharmacological inhibition of β-TRCP may provide a way of restoring REST tumor suppressor function in human cancer," the authors write.