Visit our Expo - Redox and Inflammation signaling 2012

VI. Proteasome degradation pathways Poster VI, 1
Dactylin, a F-box/WD ubiquitin ligase regulates osteoblast differentiation and limb
development
Steven Y Cheng1, 2 and Ying E. Zhang2
1 Cellogenetics. Inc., Gaithersburg, MD 20898
2 Laboratory of Cellular & Molecular Biology, National Cancer Institute, NIH,
Bethesda, MD 20892
Dactylin is a member of the F-box/WD-40 gene family, which recruit specific target proteins
through their WD-40 protein-protein binding domains for ubiquitin mediated degradation.
Disruption of the mouse dactylin gene results in the absence of central digits, underdeveloped
or absent metacarpal/metatarsal bones and syndactyly. This phenotype is remarkably similar
to split hand-split foot malformation in humans, a clinically heterogeneous condition with a
variety of modes of transmission. We found BMP signaling downregulates dactylin
expression through Smad pathways. Moreover, we showed that downregulation of Dactylin
is required for BMP-2-mediated C2C12 myoblast differentiation into osteoblast since
overexpression of Dactylin inhibited osteoblast differentiation. Thus, through its F-Box and
WD protein interaction domains, Dactylin regulates osteoblast differentiation by modulating
BMP signaling. These results offer new insights into how BMP elicits biological effects, in
particular into the mechanism of inhibition of myoblast differentiation and stimulation of
osteoblast differentiation, and important role of Dactylin in controlling mesenchymal cell fate.
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