Insight into the molecular function and transcriptional regulation of activator protein 1 (AP-1) components c-Jun/c-Fos ortholog in red lip mullet (Liza haematocheila)

• Published in: Fish & shellfish immunology Vol. 93; pp. 597 - 611
• Main Authors: Janson, N.D., Jehanathan, Nilojan, Jung, Sumi, Priyathilaka, Thanthrige Thiunuwan, Nam, Bo-Hye, Kim, Myoung-Jin, Lee, Jehee
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2019
• Subjects: Amino Acid Sequence; Animals; AP-1; c-Fos; c-Jun; Fish Diseases - immunology; Fish Proteins - chemistry; Fish Proteins - genetics; Fish Proteins - immunology; Fishes - genetics; Fishes - immunology; Gene Expression Profiling - veterinary; Gene Expression Regulation - immunology; Gram-Positive Bacterial Infections - immunology; Gram-Positive Bacterial Infections - veterinary; Immunity; Immunity, Innate - genetics; JNK; Lactococcus - physiology; Lipopolysaccharides - pharmacology; Phylogeny; Poly I-C - pharmacology; Proto-Oncogene Proteins c-fos - genetics; Proto-Oncogene Proteins c-fos - immunology; Proto-Oncogene Proteins c-jun - genetics; Proto-Oncogene Proteins c-jun - immunology; Sequence Alignment - veterinary; Transcription Factor AP-1 - chemistry; Transcription Factor AP-1 - genetics; Transcription Factor AP-1 - immunology; UV-Response; c-Fos; c-Jun; UV-Response; AP-1; Immunity; JNK
• ISSN: 1050-4648; 1095-9947
• DOI: 10.1016/j.fsi.2019.08.013

The transcription factor, activator protein-1 (AP-1), is a dimeric protein and a downstream member of the mitogen-activated protein kinase (MAPK) signaling pathway. It regulates a wide array of functions including, cell proliferation, survival, differentiation, response to UV-irradiation, immune responses, and inflammatory conditions. AP-1 belongs to the basic leucine zipper (bZIP) protein family, which consists of members from Jun, Fos, Maf, and ATF subfamilies. In the present study, c-Jun and c-Fos homologs were identified from a transcriptome database of Liza haematocheila and designated as Lhc-Jun and Lhc-Fos. In both sequences, the signature bZIP domain was identified and also the DNA binding sites, dimerization sites, as well as the phosphorylation sites, were found to be highly conserved through evolution. Tissue distribution analysis revealed that both Lhc-Jun and Lhc-Fos transcripts were ubiquitously expressed in all examined tissues of healthy mullets. In order to determine the transcriptional modulations of Lhc-Jun and Lhc-Fos, challenge experiments were carried out using LPS, poly I:C, and L. garvieae. The qRT-PCR analysis revealed significant upregulation of Lhc-Jun and Lhc-Fos in blood, gill, liver, and spleen. This is the first study that explores the correlation between UV-irradiation and AP-1 ortholog expression in teleosts. Also, this is the first time that the functional characterization of the teleost c-Fos ortholog has been carried out. Sub-cellular localization of Lhc-Jun and Lhc-Fos was observed in the nucleus. AP-1-Luc reporter assays revealed significant higher luciferase activities in both Lhc-Jun and Lhc-Fos proteins compared to mock controls. These results strongly suggest that Lhc-Jun and Lhc-Fos might play a significant role in Liza haematocheila immunity by regulating AP-1 promoter sequences in immune and stress-related genes. •Homologs of c-Jun and c-Fos were identified from Liza haematocheila (Lhc-Jun and Lhc-Fos).•Lhc-Jun and Lhc-Fos shared signature bZIP domain architecture.•Both genes were highly induced upon PAMPs and live pathogen challenges.•UV irradiation results a unique expression pattern of both genes in MK cells.•Both recombinant proteins were nuclear localized and increased the AP-1 activity.