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Atf3 links loss of epithelial polarity to defects in cell differentiation and cytoarchitecture
CD. Donohoe, G. Csordás, A. Correia, M. Jindra, C. Klein, B. Habermann, M. Uhlirova,
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
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- MeSH
- Cell Differentiation MeSH
- Chromatin Immunoprecipitation MeSH
- Drosophila melanogaster cytology genetics MeSH
- Endosomes metabolism MeSH
- Animals, Genetically Modified MeSH
- Imaginal Discs cytology physiology MeSH
- Lamin Type A genetics metabolism MeSH
- Larva MeSH
- MAP Kinase Signaling System MeSH
- Tumor Suppressor Proteins genetics metabolism MeSH
- Nucleotide Motifs physiology MeSH
- Eye growth & development MeSH
- Cell Polarity physiology MeSH
- Protein Kinase C metabolism MeSH
- Drosophila Proteins genetics metabolism MeSH
- Activating Transcription Factor 3 genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Interplay between apicobasal cell polarity modules and the cytoskeleton is critical for differentiation and integrity of epithelia. However, this coordination is poorly understood at the level of gene regulation by transcription factors. Here, we establish the Drosophila activating transcription factor 3 (atf3) as a cell polarity response gene acting downstream of the membrane-associated Scribble polarity complex. Loss of the tumor suppressors Scribble or Dlg1 induces atf3 expression via aPKC but independent of Jun-N-terminal kinase (JNK) signaling. Strikingly, removal of Atf3 from Dlg1 deficient cells restores polarized cytoarchitecture, levels and distribution of endosomal trafficking machinery, and differentiation. Conversely, excess Atf3 alters microtubule network, vesicular trafficking and the partition of polarity proteins along the apicobasal axis. Genomic and genetic approaches implicate Atf3 as a regulator of cytoskeleton organization and function, and identify Lamin C as one of its bona fide target genes. By affecting structural features and cell morphology, Atf3 functions in a manner distinct from other transcription factors operating downstream of disrupted cell polarity.
Biology Center Czech Academy of Sciences Institute of Entomology Ceske Budejovice Czech Republic
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