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

  • 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 β-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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Author:Petra Klemmt, Eduard Resch, Isabell Smyrek, Knut Engels, Ernst H. K. StelzerORCiDGND, Anna Starzinski-PowitzORCiDGND
URN:urn:nbn:de:hebis:30:3-451387
DOI:https://doi.org/10.1242/bio.019463
ISSN:2046-6390
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/27870635
Parent Title (English):Biology open
Publisher:Company
Place of publication:Cambridge
Document Type:Article
Language:English
Year of Completion:2016
Date of first Publication:2016/11/15
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2017/11/30
Tag:AJAP1; Adherence junctions; Lactation; Mammary gland; Splice variants; Tumor suppressor protein
Volume:5
Issue:11
Page Number:13
First Page:1607
Last Page:1619
Note:
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed
HeBIS-PPN:427819911
Institutes:Biowissenschaften / Biowissenschaften
Medizin / Medizin
Exzellenzcluster / Exzellenzcluster Makromolekulare Komplexe
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Open-Access-Publikationsfonds:Biowissenschaften
Licence (German):License LogoCreative Commons - Namensnennung 3.0