Essential role of Fbxl14 ubiquitin ligase in regulation of vertebrate axis formation through modulating Mkp3 level

The F-box family of proteins (FBPs), the substrate-recognition components of the Skp1-Cul1-F-box-protein (SCF) ubiquitin ligase, are evolutionarily conserved in various species and exhibit key roles in a wide array of biological processes, including tumorigenesis and development 1, 2, 3. Although approximately 70 FBPs have been identified in humans 4, 5, only a few of them have been well characterized. Fbxl14 (F-box and leucine-rich repeat protein 14) has been reported to regulate Snail2 protein during neural crest development of Xenopus laevis embryos 6 and to control Snail1 protein stability in mammalian cells 7. There are two homologs of Fbxl14 in zebrafish, namely Fbxl14a and Fbxl14b. In this study, we show that Fbxl14a and Fbxl14b are differential regulators of the dorsoventral (DV) patterning of zebrafish embryos and further demonstrate that their roles in axis formation are differentially executed through the modulation of MAP kinase phosphatase-3 (Mkp3) ubiquitination and protein levels.