Donohoe, Colin D., Csordas, Gabor ORCID: 0000-0001-6871-6839, Correia, Andreia, Jindra, Marek ORCID: 0000-0002-2196-9924, Klein, Corinna, Habermann, Bianca and Uhlirova, Mirka (2018). Atf3 links loss of epithelial polarity to defects in cell differentiation and cytoarchitecture. PLoS Genet., 14 (3). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1553-7404

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Abstract

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 DIg1 induces atf3 expression via aPKC but independent of Jun-N-terminal kinase (JNK) signaling. Strikingly, removal of Atf3 from DIg1 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Donohoe, Colin D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Csordas, GaborUNSPECIFIEDorcid.org/0000-0001-6871-6839UNSPECIFIED
Correia, AndreiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jindra, MarekUNSPECIFIEDorcid.org/0000-0002-2196-9924UNSPECIFIED
Klein, CorinnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Habermann, BiancaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Uhlirova, MirkaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-194145
DOI: 10.1371/journal.pgen.1007241
Journal or Publication Title: PLoS Genet.
Volume: 14
Number: 3
Date: 2018
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1553-7404
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ACTIVATING TRANSCRIPTION FACTOR-3; SIGNALING PATHWAY; TUMOR SUPPRESSION; DROSOPHILA; JUNCTIONS; CANCER; GROWTH; EXPRESSION; NETWORK; PROTEINMultiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/19414

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