Gain-of-function mutation in ADULT syndrome reveals the presence of a second transactivation domain in p63
| Autor: | Han G. Brunner, Frank McKeon, Waltraut Friedl, Elmar Krieger, Kaate R.J. Vanmolkot, Pascal H.G. Duijf, Peter Propping, Hans van Bokhoven, Volker Dötsch |
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| Rok vydání: | 2002 |
| Předmět: |
Models
Molecular Transcriptional Activation Gene isoform Ectodermal dysplasia Protein Conformation Elucidation of hereditary disorders and their molecular diagnosis Mutation Missense Biology medicine.disease_cause Transactivation chemistry.chemical_compound Genetics medicine Humans Abnormalities Multiple Genes Tumor Suppressor Molecular Biology Gene Transcription factor Genetics (clinical) Mutation integumentary system Tumor Suppressor Proteins Membrane Proteins Syndrome General Medicine DNA-binding domain Phosphoproteins medicine.disease Protein Structure Tertiary DNA-Binding Proteins stomatognathic diseases chemistry Trans-Activators Opheldering van erfelijke ziekten en hun moleculaire diagnostiek DNA Transcription Factors |
| Zdroj: | Human Molecular Genetics, 11, 799-804 Human Molecular Genetics, 11, 7, pp. 799-804 Scopus-Elsevier |
| ISSN: | 0964-6906 |
| Popis: | Item does not contain fulltext The transcriptional co-activator p63 is of crucial importance for correct development of the limbs, ectodermal appendages (skin, nails, teeth, hair, glands), lip and palate. Mutations in the p63 gene are found in a number of human syndromes, including ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) syndrome, limb-mammary syndrome (LMS), Hay-Wells syndrome and in non-syndromic split-hand/split-foot malformation (SHFM). Each syndrome has a specific pattern of mutations with different functional effects in in vitro functional assays. We report a mutation R298Q in acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome, another EEC-like condition. The mutation is located in the DNA binding domain of p63, which harbors almost all EEC associated mutations. However, unlike mutations in EEC syndrome, the R298Q ADULT syndrome mutation does not impair DNA binding. Rather, the mutation confers novel transcription activation capacity on the DeltaN-p63gamma isoform, which normally does not possess such activity. These results confirm that ADULT syndrome is a clinically as well as molecularly distinct member of the expanding p63 mutation family of human malformation syndromes. Our results further show that p63 contains a second transactivation domain which is normally repressed and can become activated by mutations in the DNA binding domain of p63. |
| Databáze: | OpenAIRE |
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