WNT3-WNT14B and WNT3A-WNT14 gene clusters (Review).
WNT signals are transduced to beta-catenin - TCF pathway, JNK pathway, or Ca2+-releasing pathway through WNT receptors. FRAT1, FRAT2, and PAR-1 are positive regulators of WNT - beta-catenin pathway. APC, AXIN, NKD1, NKD2, and Strabismus (STB1, STB2) are negative regulators of WNT - beta-catenin pathway. Here, biological significance of WNT3-WNT14B/WNT15 gene cluster (human chromosome 17q21) and WNT3A-WNT14 gene cluster (human chromosome 1q42) will be reviewed. Total-amino-acid identity between WNT3 and WNT3A is 84.2%, and that between WNT14 and WNT14B is 61.4%. WNT3A and WNT14B show reciprocal regulation by all-trans retinoic acid in NT2 cells and by beta-estradiol in MCF-7 cells. Exon-intron structures are well conserved between WNT3-WNT14B gene cluster and WNT3A-WNT14 gene cluster, except for the existence of an additional intron in 3'-UTR of WNT3. Capicua pseudogene and AK024248-related sequence are located within intergenic region of human WNT3A-WNT14 gene cluster, but not within intergenic regions of human WNT3-WNT14B gene cluster and mouse Wnt3a-Wnt14 gene cluster. Integration of mouse mammary tumor virus (MMTV) into mouse Wnt3-Wnt14b gene cluster leads to carcinogenesis. Because these WNT gene clusters might be fragile sites in the human genome, implication of WNT3 or WNT3A in cancer as well as implication of WNT14 or WNT14B in connective tissue disease and congenital joint malformation should be elucidated in the future. WNT3, WNT3A, WNT14, and WNT14B might be applicable to tissue engineering of neuron and joint in the field of regenerative medicine, and as an early diagnostic marker in the field of clinical oncology.
Katoh
Masaru
M
Genetics and Cell Biology Section, Genetics Division, National Cancer Center Research Institute, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. mkatoh@ncc.go.jp
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002874:Chromosome Mapping; D006023:Glycoproteins; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D005810:Multigene Family; D009369:Neoplasms / Q000378:metabolism; D011506:Proteins / Q000235:genetics*; D015398:Signal Transduction; D013997:Time Factors; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein
D006023:Glycoproteins; D011506:Proteins; C555507:WNT3 protein, human; C555510:WNT3A protein, human; C110670:WNT9A protein, human; C449090:WNT9B protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein; C555508:Wnt3 protein, mouse; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; C486388:Wnt9a protein, mouse; D002118:Calcium