Ubiquitin ligase COP1 coordinates transcriptional programs that control cell type specification in the developing mouse brain.

ABSTRACT: The E3 ubiquitin ligase CRL4^COP1/DET1 is active in the absence of ERK signaling, modifying the transcription factors ETV1, ETV4, ETV5, and c-JUN with polyubiquitin that targets them for proteasomal degradation. Here we show that this posttranslational regulatory mechanism is active in neurons, with ETV5 and c-JUN accumulating within minutes of ERK activation. Mice with constitutive photomorphogenesis 1 (Cop1) deleted in neural stem cells showed abnormally elevated expression of ETV1, ETV4, ETV5, and c-JUN in the developing brain and spinal cord. Expression of c-JUN target genes Vimentin and Gfap was increased, whereas ETV5 and c-JUN both contributed to an expanded number of cells expressing genes associated with gliogenesis, including Olig1,

SUBMITTER: Newton K 

PROVIDER: S-EPMC6217379 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature