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- Title
The E3 ubiquitin ligase Wwp2 regulates craniofacial development through mono-ubiquitylation of Goosecoid.
- Authors
Weiguo Zou; Xi Chen; Jae-Hyuck Shim; Zhiwei Huang; Brady, Nicholas; Hu, Dorothy; Drapp, Rebecca; Sigrist, Kirsten; Glimcher, Laurie H.; Jones, Dallas
- Abstract
Craniofacial anomalies (CFAs) are the most frequently occurring human congenital disease, and a major cause of infant mortality and childhood morbidity. Although CFAs seems to arise from a combination of genetic factors and environmental influences, the underlying gene defects and pathophysiological mechanisms for most CFAs are currently unknown. Here we reveal a role for the E3 ubiquitin ligase Wwp2 in regulating craniofacial patterning. Mice deficient in Wwp2 develop malformations of the craniofacial region. Wwp2 is present in cartilage where its expression is controlled by Sox9. Our studies demonstrate that Wwp2 influences craniofacial patterning through its interactions with Goosecoid (Gsc), a paired-like homeobox transcription factor that has an important role in craniofacial development. We show that Wwp2-associated Gsc is a transcriptional activator of the key cartilage regulatory protein Sox6. Wwp2 interacts with Gsc to facilitate its mono-ubiquitylation, a post-translational modification required for optimal transcriptional activation of Gsc. Our results identify for the first time a physiological pathway regulated by Wwp2 in vivo, and also a unique non-proteolytic mechanism through which Wwp2 controls craniofacial development.
- Subjects
UBIQUITIN; LIGASES; HOMEOBOX genes; GENETIC disorders; INFANT mortality; ENZYMES
- Publication
Nature Cell Biology, 2011, Vol 13, Issue 1, p59
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/ncb2134