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Wnt Modification by Tiki Proteins
Author(s) -
He Xi
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.236.1
Subject(s) - wnt signaling pathway , xenopus , biology , microbiology and biotechnology , lrp6 , zebrafish , transmembrane protein , signal transduction , receptor , genetics , gene
We focus on understanding the molecular mechanism of Wnt signaling in vertebrate development, stem cell regulation, and human cancer and diseases. We are interested in canonical Wnt/b‐catenin signaling and noncanonical Wnt signaling pathways. We employ molecular, structural, cellular, and developmental approaches in Xenopus, mice, and human cell culture. Using functional cDNA expression screening, we identified Tiki1, a transmembrane protein that is expressed specifically in the Spemann‐Mangold Organizer in Xenopus embryos and is required for anterior development. Tiki1 antagonizes Wnt function by acting as a metalloprotease to cleave a few amino terminal residues of a Wnt protein, resulting in oxidized Wnt oligomers that exhibit normal secretion but minimized receptor‐binding capability. Tiki1 is the first known Wnt inactivating enzyme, and is conserved from invertebrates to vertebrates including humans. I will discuss our ongoing study of the function, Wnt cleavage specificity and regulation of Tiki proteins.