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

• Verfasst von: Rao, Ercole [VerfasserIn]
• Verfasst von: Blaschke, Rüdiger Jörg [VerfasserIn]
• Verfasst von: Marchini, Antonio [VerfasserIn]
• Verfasst von: Niesler, Beate [VerfasserIn]
• Verfasst von: Burnette, Michael H. [VerfasserIn]
• Verfasst von: Rappold, Gudrun [VerfasserIn]
• Titel: The Leri-Weill and Turner syndrome homeobox gene SHOX encodes a cell-type specific transcriptional activator
• Verf.angabe: Ercole Rao, Rüdiger J. Blaschke, Antonio Marchini, Beate Niesler, Michael Burnett and Gudrun A. Rappold
• E-Jahr: 2001
• Jahr: 15 December 2001
• Umfang: 10 S.
• Teil: volume:10
• Teil: year:2001
• Teil: number:26
• Teil: pages:3083-3091
• Teil: extent:10
• Fussnoten: Gesehen am 07.04.2021
• Titel Quelle: Enthalten in: Human molecular genetics
• Ort Quelle: Oxford : Oxford Univ. Press, 1992
• Jahr Quelle: 2001
• Band/Heft Quelle: 10(2001), 26, Seite 3083-3091
• ISSN Quelle: 1460-2083
• DOI: doi:10.1093/hmg/10.26.3083
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1753235162

Abstract

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.