Gain-of-function mutation in ADULT syndrome reveals the presence of a second transactivation domain in p63.

Gain-of-function mutation in ADULT syndrome reveals the presence of a second transactivation domain in p63. Research Abstract Details 

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Gain-of-function mutation in ADULT syndrome reveals the presence of a second transactivation domain in p63. Abstract Text:

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.

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Gain-of-function mutation in ADULT syndrome reveals the presence of a second transactivation domain in p63. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Human molecular genetics

VOLUME: 11

Page Numbers: 799-804

Journal Abbreviation: Hum. Mol. Genet.

ISSN: 0964-6906

DAY: 1

MONTH: Apr

YEAR: 2002

Gain-of-function mutation in ADULT syndrome reveals the presence of a second transactivation domain in p63. Information

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LANGUAGE: eng

NlmUniqueID: 9208958

Gain-of-function mutation in ADULT syndrome reveals the presence of a second transactivation domain in p63. Keywords Mesh Terms:

KEYWORDS: Tumor Suppressor Proteins

MESH TERMS: genetics

Chemical & Substance for Abstract: Gain-of-function mutation in ADULT syndrome reveals the presence of a second transactivation domain in p63. Information

Substance Name: Tumor Suppressor Proteins

Registry Number: 0

Grant and Affiliation Information for Gain-of-function mutation in ADULT syndrome reveals the presence of a second transactivation domain in p63.

AFFILIATION: Department of Human Genetics 417, University Medical Centre Nijmegen, Box 9101, 6500 HB Nijmegen, The Netherlands.

Country: England

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MEDLINETA: Hum Mol Genet

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