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XB-ART-51292
Nature September 24, 2015; 525 (7570): 523-7.

Cell-fate determination by ubiquitin-dependent regulation of translation.

Werner A , Iwasaki S , McGourty CA , Medina-Ruiz S , Teerikorpi N , Fedrigo I , Ingolia NT , Rape M .


Abstract
Metazoan development depends on the accurate execution of differentiation programs that allow pluripotent stem cells to adopt specific fates. Differentiation requires changes to chromatin architecture and transcriptional networks, yet whether other regulatory events support cell-fate determination is less well understood. Here we identify the ubiquitin ligase CUL3 in complex with its vertebrate-specific substrate adaptor KBTBD8 (CUL3(KBTBD8)) as an essential regulator of human and Xenopus tropicalis neural crest specification. CUL3(KBTBD8) monoubiquitylates NOLC1 and its paralogue TCOF1, the mutation of which underlies the neurocristopathy Treacher Collins syndrome. Ubiquitylation drives formation of a TCOF1-NOLC1 platform that connects RNA polymerase I with ribosome modification enzymes and remodels the translational program of differentiating cells in favour of neural crest specification. We conclude that ubiquitin-dependent regulation of translation is an important feature of cell-fate determination.

PubMed ID: 26399832
PMC ID: PMC4602398
Article link: Nature
Grant support: [+]

Species referenced: Xenopus
Genes referenced: acta2 acta4 actc1 arrb1 arrb2 brd2 casp3.2 cul3 kbtbd8 nolc1 rpl28 smo tcof1 tp53
Morpholinos: cul3 MO1 kbtbd8 MO1 kbtbd8 MO2


Article Images: [+] show captions
References [+] :
, Positional cloning of a gene involved in the pathogenesis of Treacher Collins syndrome. The Treacher Collins Syndrome Collaborative Group. 1996, Pubmed