TBX-2 paper CMLS v10_inidgo.pdf (14.51 MB)
Download fileFunction of the C. elegans T-box factor TBX-2 depends on SUMOylation
journal contribution
posted on 2015-09-21, 00:00 authored by Paul Huber, Tanya Crum, Lynn M. Clary, Tom Ronan, Adelaide V. Packard, Peter G. OkkemaT-box transcription factors are critical developmental regulators in all multi-cellular organisms,
and altered T-box factor activity is associated with a variety of human congenital diseases and
cancers. Despite the biological significance of T-box factors, their mechanism of action is not
well understood. Here we examine whether SUMOylation affects the function of the C. elegans
Tbx2 sub-family T-box factor TBX-2. We have previously shown that TBX-2 interacts with the
E2 SUMO-conjugating enzyme UBC-9, and that loss of TBX-2 or UBC-9 produces identical
defects in ABa derived pharyngeal muscle development. We now show that TBX-2 is
SUMOylated in mammalian cell assays, and that both UBC-9 interaction and SUMOylation
depends on two SUMO consensus sites located in the T-box DNA binding domain and near the
TBX-2 C-terminus, respectively. In co-transfection assays, a TBX-2:GAL4 fusion protein
represses expression of a 5xGal4:tk:luciferase construct. However, this activity does not
require SUMOylation, indicating SUMO is not generally required for TBX-2 repressor activity. In
C. elegans, reducing SUMOylation enhances the phenotype of a temperature sensitive tbx-2
mutant and results in ectopic expression of a gene normally repressed by TBX-2, demonstrating
that SUMOylation is important for TBX-2 function in vivo. Finally, we show mammalian
orthologs of TBX-2, Tbx2 and Tbx3, can also be SUMOylated, suggesting SUMOylation may be
a conserved mechanism controlling T-box factor activity.