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Miz1 Deficiency in the Mammary Gland Causes a Lactation Defect by Attenuated Stat5 Expression and Phosphorylation

Please always quote using this URN: urn:nbn:de:bvb:20-opus-117286
  • Miz1 is a zinc finger transcription factor with an N-terminal POZ domain. Complexes with Myc, Bcl-6 or Gfi-1 repress expression of genes like Cdkn2b (p15(Ink4)) or Cd-kn1a (p21(Cip1)). The role of Miz1 in normal mammary gland development has not been addressed so far. Conditional knockout of the Miz1 POZ domain in luminal cells during pregnancy caused a lactation defect with a transient reduction of glandular tissue, reduced proliferation and attenuated differentiation. This was recapitulated in vitro using mouse mammary gland derived HC11Miz1 is a zinc finger transcription factor with an N-terminal POZ domain. Complexes with Myc, Bcl-6 or Gfi-1 repress expression of genes like Cdkn2b (p15(Ink4)) or Cd-kn1a (p21(Cip1)). The role of Miz1 in normal mammary gland development has not been addressed so far. Conditional knockout of the Miz1 POZ domain in luminal cells during pregnancy caused a lactation defect with a transient reduction of glandular tissue, reduced proliferation and attenuated differentiation. This was recapitulated in vitro using mouse mammary gland derived HC11 cells. Further analysis revealed decreased Stat5 activity in Miz1 Delta POZ mammary glands and an attenuated expression of Stat5 targets. Gene expression of the Prolactin receptor (PrlR) and ErbB4, both critical for Stat5 phosphorylation (pStat5) or pStat5 nuclear translocation, was decreased in Miz1 Delta POZ females. Microarray, ChIP-Seq and gene set enrichment analysis revealed a down-regulation of Miz1 target genes being involved in vesicular transport processes. Our data suggest that deranged intracellular transport and localization of PrlR and ErbB4 disrupt the Stat5 signalling pathway in mutant glands and cause the observed lactation phenotype.show moreshow less

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Metadaten
Author: Adrian Sanz-Moreno, David Fuhrmann, Elmar Wolf, Björn von Eyss, Martin Eilers, Hans-Peter Elsässer
URN:urn:nbn:de:bvb:20-opus-117286
Document Type:Journal article
Faculties:Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):PLOS ONE
Year of Completion:2014
Volume:9
Issue:2
Pagenumber:e89187
Source:PLoS ONE 9(2): e89187. doi:10.1371/journal.pone.0089187
DOI:https://doi.org/10.1371/journal.pone.0089187
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=24586582
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Tag:C-MYC; breast-cancer cells; differentiation; epithelial cells; gene expression; growth; prolactin; proliferation; transcription factor MIZ-1; transgenic mice
Release Date:2015/08/18
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung