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SUMOylation of DLX3 by SUMO1 promotes its transcriptional activity
Author(s) -
Duverger Olivier,
Chen Susie X.,
Lee Delia,
Li Tianwei,
Chock P. Boon,
Morasso Maria I.
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22891
Subject(s) - sumo protein , microbiology and biotechnology , chemistry , computational biology , biology , genetics , gene , ubiquitin
Small ubiquitin‐like modifiers (SUMO) are post‐translational modifiers that regulate target protein activity in diverse ways. The most common group of SUMO substrates is transcription factors, whose transcriptional activity can be altered positively or negatively as a result of SUMOylation. DLX3 is a homeodomain transcription factor involved in placental development, in the differentiation of structures involving epithelial‐mesenchymal interactions, such as hair, teeth and nails, and in bone mineralization. We identified two potential SUMOylation sites in the N‐terminal domain of DLX3 at positions K83 and K112. Among the six members of the Distal‐less family, DLX3 is the only member containing these sites, which are highly conserved among vertebrates. Co‐expression experiments demonstrated that DLX3 can be SUMOylated by SUMO1. Site‐directed mutagenesis of lysines 83 and 112 to arginines (K83R and K112R) demonstrated that only K112 is involved in SUMOylation. Immunocytochemical analysis determined that SUMOylation does not affect DLX3 translocation to the nucleus and favors perinuclear localization. Moreover, using electrophoresis mobility shift assay (EMSA), we found that DLX3 is still able to bind DNA when SUMOylated. Using luciferase reporter assays, we showed that DLX3 K112R exhibits a significantly lower transcriptional activity compared to DLX3 WT , suggesting that SUMOylation has a positive effect on DLX3 activity. We identified a new level of regulation in the activity of DLX3 that may play a crucial role in the regulation of hair, teeth, and bone development. J. Cell. Biochem. 112: 445–452, 2011. © 2010 Wiley‐Liss, Inc.