A novel 9-amino-acid transactivation domain in the C-terminal part of Sox18.
Sox transcription factors are members of the Sry-related protein family that play multiple roles mainly during development. Sox18 has been implicated in the development of hair follicles as well as the blood and lymphatic vasculature, due to the identification of mutations that result in the ragged phenotype in mice, and in the hypotrichosis lymphedema telangiectasia syndrome in humans. Sox18 consists of an N-terminal high-mobility group DNA binding and a central transactivation domain, followed by a C-terminal region of unknown function. We show here that this C-terminal domain consists of three blocks that are highly conserved within a subgroup of the Sox family, and that the central so-called charged block comprises an additional strong transactivating domain. This activity can be pinpointed to a recently described 9aa transactivation motif that mediates the interaction with the transcriptional cofactor TAF9. These result can explain previously controversial data on the functional consequences of Sox18 mutations in mice and humans.
Sandholzer
Julia
J
Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, A-1090 Vienna, Lazarettg 19, Austria.
Hoeth
Martina
M
Piskacek
Martin
M
Mayer
Herbert
H
de Martin
Rainer
R
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D006609:High Mobility Group Proteins / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D055760:SOXF Transcription Factors; D020539:Sequence Analysis, Protein / Q000379:methods*; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*
D000596:Amino Acids; D006609:High Mobility Group Proteins; C095473:SOX18 protein, human; D055760:SOXF Transcription Factors; D014157:Transcription Factors