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Publication : Alternative exon usage creates novel transcript variants of tumor suppressor SHREW-1 gene with differential tissue expression profile.

First Author  Klemmt PA Year  2016
Journal  Biol Open Volume  5
Issue  11 Pages  1607-1619
PubMed ID  27870635 Mgi Jnum  J:237197
Mgi Id  MGI:5811687 Doi  10.1242/bio.019463
Citation  Klemmt PA, et al. (2016) Alternative exon usage creates novel transcript variants of tumor suppressor SHREW-1 gene with differential tissue expression profile. Biol Open 5(11):1607-1619
abstractText  Shrew-1, also called AJAP1, is a transmembrane protein associated with E-cadherin-mediated adherence junctions and a putative tumor suppressor. Apart from its interaction with beta-catenin and involvement in E-cadherin internalization, little structure or function information exists. Here we explored shrew-1 expression during postnatal differentiation of mammary gland as a model system. Immunohistological analyses with antibodies against either the extracellular or the cytoplasmic domains of shrew-1 consistently revealed the expression of full-length shrew-1 in myoepithelial cells, but only part of it in luminal cells. While shrew-1 localization remained unaltered in myoepithelial cells, nuclear localization occurred in luminal cells during lactation. Based on these observations, we identified two unknown shrew-1 transcript variants encoding N-terminally truncated proteins. The smallest shrew-1 protein lacks the extracellular domain and is most likely the only variant present in luminal cells. RNA analyses of human tissues confirmed that the novel transcript variants of shrew-1 exist in vivo and exhibit a differential tissue expression profile. We conclude that our findings are essential for the understanding and interpretation of future functional and interactome analyses of shrew-1 variants.
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