RRC ID 52720
著者 Satou Y, Minami K, Hosono E, Okada H, Yasuoka Y, Shibano T, Tanaka T, Taira M.
タイトル Phosphorylation states change Otx2 activity for cell proliferation and patterning in the Xenopus embryo.
ジャーナル Development
Abstract The homeodomain transcription factor Otx2 has essential roles in head and eye formation via the negative and positive regulation of its target genes, but it remains elusive how this dual activity of Otx2 affects cellular functions. In the current study, we first demonstrated that both exogenous and endogenous Otx2 are phosphorylated at multiple sites. Using Xenopus embryos, we identified three possible cyclin-dependent kinase (Cdk) sites and one Akt site, and analyzed the biological activities of phosphomimetic (4E) and nonphosphorylatable (4A) mutants for those sites. In the neuroectoderm, the 4E but not the 4A mutant downregulated the Cdk inhibitor gene p27xic1 (cdknx) and posterior genes, and promoted cell proliferation, possibly forming a positive-feedback loop consisting of Cdk, Otx2 and p27xic1 for cell proliferation, together with anteriorization. Conversely, the 4A mutant functioned as an activator on its own and upregulated the expression of eye marker genes, resulting in enlarged eyes. Consistent with these results, the interaction of Otx2 with the corepressor Tle1 is suggested to be phosphorylation dependent. These data suggest that Otx2 orchestrates cell proliferation, anteroposterior patterning and eye formation via its phosphorylation state.
巻・号 145(5)
公開日 2018-3-12
DOI 10.1242/dev.159640
PII dev.159640
PMID 29440302
MeSH Animals Animals, Genetically Modified Body Patterning* / genetics Cell Proliferation* Cyclin-Dependent Kinases / metabolism Embryo, Nonmammalian Eye / embryology Eye / metabolism Gene Expression Regulation, Developmental Oncogene Protein v-akt / metabolism Otx Transcription Factors / metabolism* Phosphorylation Protein Processing, Post-Translational Xenopus laevis / embryology* Xenopus laevis / genetics Xenopus laevis / metabolism*
IF 5.611
引用数 1
リソース情報
ツメガエル・イモリ Xenopus tropicalis