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The E3 ubiquitin ligase Wwp2 regulates craniofacial development through monoubiquitination of Goosecoid
Craniofacial anomalies (CFA) are the most frequent human congenital disease and a major cause of infant mortality and childhood morbidity. Although CFA appear to arise from a combination of genetic factors and environmental influences, the underlying gene defects and pathomechanisms for the majority...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3059716/ https://www.ncbi.nlm.nih.gov/pubmed/21170031 http://dx.doi.org/10.1038/ncb2134 |
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author | Zou, Weiguo Chen, Xi Shim, Jae Huang, Zhiwei Brady, Nicholas Hu, Dorothy Drapp, Rebecca Sigrist, Kirsten Glimcher, Laurie H. Jones, Dallas |
author_facet | Zou, Weiguo Chen, Xi Shim, Jae Huang, Zhiwei Brady, Nicholas Hu, Dorothy Drapp, Rebecca Sigrist, Kirsten Glimcher, Laurie H. Jones, Dallas |
author_sort | Zou, Weiguo |
collection | PubMed |
description | Craniofacial anomalies (CFA) are the most frequent human congenital disease and a major cause of infant mortality and childhood morbidity. Although CFA appear to arise from a combination of genetic factors and environmental influences, the underlying gene defects and pathomechanisms for the majority of CFA are currently unknown. Here we reveal an unknown role for the E3 ubiquitin ligase Wwp2 in regulating craniofacial patterning. Mice deficient for 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 plays 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-ubiquitination, a post-translational modification required for optimal transcriptional activation of Gsc. Our results identify the first physiological pathway regulated by Wwp2 in vivo as well as identify a unique non-proteolytic mechanism through which the Wwp2 controls craniofacial development. |
format | Text |
id | pubmed-3059716 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
record_format | MEDLINE/PubMed |
spelling | pubmed-30597162011-07-01 The E3 ubiquitin ligase Wwp2 regulates craniofacial development through monoubiquitination of Goosecoid Zou, Weiguo Chen, Xi Shim, Jae Huang, Zhiwei Brady, Nicholas Hu, Dorothy Drapp, Rebecca Sigrist, Kirsten Glimcher, Laurie H. Jones, Dallas Nat Cell Biol Article Craniofacial anomalies (CFA) are the most frequent human congenital disease and a major cause of infant mortality and childhood morbidity. Although CFA appear to arise from a combination of genetic factors and environmental influences, the underlying gene defects and pathomechanisms for the majority of CFA are currently unknown. Here we reveal an unknown role for the E3 ubiquitin ligase Wwp2 in regulating craniofacial patterning. Mice deficient for 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 plays 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-ubiquitination, a post-translational modification required for optimal transcriptional activation of Gsc. Our results identify the first physiological pathway regulated by Wwp2 in vivo as well as identify a unique non-proteolytic mechanism through which the Wwp2 controls craniofacial development. 2010-12-19 2011-01 /pmc/articles/PMC3059716/ /pubmed/21170031 http://dx.doi.org/10.1038/ncb2134 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Zou, Weiguo Chen, Xi Shim, Jae Huang, Zhiwei Brady, Nicholas Hu, Dorothy Drapp, Rebecca Sigrist, Kirsten Glimcher, Laurie H. Jones, Dallas The E3 ubiquitin ligase Wwp2 regulates craniofacial development through monoubiquitination of Goosecoid |
title | The E3 ubiquitin ligase Wwp2 regulates craniofacial development through monoubiquitination of Goosecoid |
title_full | The E3 ubiquitin ligase Wwp2 regulates craniofacial development through monoubiquitination of Goosecoid |
title_fullStr | The E3 ubiquitin ligase Wwp2 regulates craniofacial development through monoubiquitination of Goosecoid |
title_full_unstemmed | The E3 ubiquitin ligase Wwp2 regulates craniofacial development through monoubiquitination of Goosecoid |
title_short | The E3 ubiquitin ligase Wwp2 regulates craniofacial development through monoubiquitination of Goosecoid |
title_sort | e3 ubiquitin ligase wwp2 regulates craniofacial development through monoubiquitination of goosecoid |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3059716/ https://www.ncbi.nlm.nih.gov/pubmed/21170031 http://dx.doi.org/10.1038/ncb2134 |
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