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The Leri-Weill and Turner syndrome homeobox gene SHOX encodes a cell-type specific transcriptional activator

Functional impairment of the human homeobox gene SHOX causes short stature and Madelung deformity in Leri-Weill syndrome (LWS) and has recently been implicated in additional skeletal malformations frequently observed in Turner syndrome. To enhance our understanding of the underlying mechanism of act...

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Bibliographische Detailangaben
Hauptverfasser: Rao, Ercole (VerfasserIn) , Blaschke, Rüdiger Jörg (VerfasserIn) , Marchini, Antonio (VerfasserIn) , Niesler, Beate (VerfasserIn) , Burnette, Michael H. (VerfasserIn) , Rappold, Gudrun (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 15 December 2001
In: Human molecular genetics
Year: 2001, Jahrgang: 10, Heft: 26, Pages: 3083-3091
ISSN:1460-2083
DOI:10.1093/hmg/10.26.3083
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/hmg/10.26.3083
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Verfasserangaben:Ercole Rao, Rüdiger J. Blaschke, Antonio Marchini, Beate Niesler, Michael Burnett and Gudrun A. Rappold
Beschreibung
Zusammenfassung:Functional impairment of the human homeobox gene SHOX causes short stature and Madelung deformity in Leri-Weill syndrome (LWS) and has recently been implicated in additional skeletal malformations frequently observed in Turner syndrome. To enhance our understanding of the underlying mechanism of action, we have established a cell culture model consisting of four stably transfected cell lines and analysed the functional properties of the SHOX protein on a molecular level. Results show that the SHOX-encoded protein is located exclusively within the nucleus of a variety of cell lines, including U2Os, HEK293, COS7 and NIH 3T3 cells. In contrast to this cell-type independent nuclear translocation, the transactivating potential of the SHOX protein on different luciferase reporter constructs was observed only in the osteogenic cell line U2Os. Since C-terminally truncated forms of SHOX lead to LWS and idiopathic short stature, we have compared the activity of wild-type and truncated SHOX proteins. Interestingly, C-terminally truncated SHOX proteins are inactive with regards to target gene activation. These results for the first time provide an explanation of SHOX-related phenotypes on a molecular level and suggest the existence of qualitative trait loci modulating SHOX activity in a cell-type specific manner.
Beschreibung:Gesehen am 07.04.2021
Beschreibung:Online Resource
ISSN:1460-2083
DOI:10.1093/hmg/10.26.3083

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