Universität zu Köln

Rynes, Jan, Donohoe, Colin D., Frommolt, Peter ORCID: 0000-0002-1966-8014, Brodesser, Susanne, Jindra, Marek ORCID: 0000-0002-2196-9924 and Uhlirova, Mirka ORCID: 0000-0002-5735-8287 (2012). Activating Transcription Factor 3 Regulates Immune and Metabolic Homeostasis. Mol. Cell. Biol., 32 (19). S. 3949 - 3963. WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 0270-7306

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Abstract

Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-kappa B/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rynes, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Donohoe, Colin D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Frommolt, Peter UNSPECIFIED orcid.org/0000-0002-1966-8014 UNSPECIFIED Brodesser, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Jindra, Marek UNSPECIFIED orcid.org/0000-0002-2196-9924 UNSPECIFIED Uhlirova, Mirka UNSPECIFIED orcid.org/0000-0002-5735-8287 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-482148
DOI:	10.1128/MCB.00429-12
Journal or Publication Title:	Mol. Cell. Biol.
Volume:	32
Number:	19
Page Range:	S. 3949 - 3963
Date:	2012
Publisher:	AMER SOC MICROBIOLOGY
Place of Publication:	WASHINGTON
ISSN:	0270-7306
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DROSOPHILA-MELANOGASTER; PERITROPHIC MATRIX; GENE-EXPRESSION; IKK-BETA; KAPPA-B; MOLECULAR-MECHANISMS; BACTERIAL-INFECTION; NEGATIVE REGULATOR; INSULIN-RESISTANCE; LIVER DYSFUNCTION Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48214