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Tricho-dento-osseous Syndrome Mutant Dlx3 Shows Lower Transactivation Potential but Has Longer Half-life than Wild-type Dlx3

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Authors
Cha, Ji Hun; Ryoo, Hyun-Mo; Woo, Kyung Mi; Kim, Gwan-Shik; Baek, Jeong-Hwa
Issue Date
2007-12
Publisher
Korean Acadamy of Oral Biology
Citation
International Journal of Oral Biology 32: 119-125
Abstract
Dlx3 is a homeodomain protein and is known to play a role
in development and differentiation of many tissues. Deletion
of four base pairs in DLX3 (NT3198) is causally related to
tricho-dento-osseous (TDO) syndrome (OMIM #190320), a
genetic disorder manifested by taurodontism, hair abnormalities,
and increased bone density in the cranium. The
molecular mechanisms that explain the phenotypic characteristics
of TDO syndrome have not been clearly determined.
In this study, we examined phenotypic characteristics of
wild type DLX3 (wtDlx3) and 4-BP DEL DLX3 (TDO mtDlx3)
in C2C12 cells. To investigate how wtDlx3 and TDO mtDlx3
differentially regulate osteoblastic differentiation, reporter
assays were performed by using luciferase reporters containing
the promoters of alkaline phosphatase, bone sialoprotein or
osteocalcin. Both wtDlx3 and TDO mtDlx3 enhanced
significantly all the reporter activities but the effect of
mtDlx3 was much weaker than that of wtDlx3. In spite of
these differences in reporter activity, electrophoretic mobility
shift assay showed that both wtDlx3 and TDO mtDlx3
formed similar amounts of DNA binding complexes with
Dlx3 binding consensus sequence or with ALP promoter
oligonucleotide bearing the Dlx3 binding core sequence.
TDO mtDlx3 exhibits a longer half-life than wtDlx3 and it
corresponds to PESTfind analysis result showing that
potential PEST sequence was missed in carboxy terminal of
TDO mtDlx3. In addition, co-immunoprecipitation demonstrated
that TDO mtDlx3 binds to Msx2 more strongly than
wtDlx3. Taken together, though TDO mtDlx3 acted as a
weaker transcriptional activator than wtDlx3 in osteoblastic cells, there is possibility that during in vivo osteoblast
differentiation TDO mtDlx3 may antagonize transcriptional
repressor activity of Msx2 more effectively and for longer
period than wtDlx3, resulting in enhancement of osteoblast
differentiation.
ISSN
1226-7155
Language
English
URI
https://hdl.handle.net/10371/69652
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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