title: NFκB and STAT3 synergistically activate the expression of FAT10, a gene counteracting the tumor suppressor p53.
abstract: Chronic inflammation is one of the main causes of cancer, yet the molecular mechanism underlying this effect is not fully understood. In this study, we identified FAT10 as a potential target gene of STAT3, the expression of which is synergistically induced by NFκB co-stimulation. STAT3 binding stabilizes NFκB on the FAT10 promoter and leads to maximum induction of FAT10 gene expression. Increased FAT10 represses the transcriptional activity of the tumor suppressor p53, a protein that accelerates the protein degradation of FAT10. This FAT10-p53 double-negative regulation is critical in the control of tumorigenesis, as overexpressed FAT10 facilitates the tumor progression in the solid tumor model. In conclusion, transcriptional synergy between STAT3 and NFκB functions to put weight on FAT10 in the mutually inhibitory FAT10-p53 regulatory loop and thus favors tumorigenesis under inflammatory conditions.
authors: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors: Yongwook
authors: Y
authors: Choi
authors: European Bioinformatics Institute, Wellcome Trust Genome Sciences Campus, Cambridge, UK.
authors: Jong Kyoung
authors: JK
authors: Kim
authors: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea. Electronic address: jyoo@postech.ac.kr.
authors: Joo-Yeon
authors: JY
authors: Yoo
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology*; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology; D011401:Promoter Regions, Genetic; D050794:STAT1 Transcription Factor / Q000276:immunology*; D050796:STAT3 Transcription Factor / Q000276:immunology*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014452:Ubiquitins / Q000235:genetics*
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D016159:Tumor Suppressor Protein p53; C109184:UBD protein, human; D014452:Ubiquitins
keywords: FAT10; Inflammation; STAT3; Tumorigenesis; p53