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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.

SUBMITTER: Choi Y

PROVIDER: S-EPMC5528625 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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NFκB and STAT3 synergistically activate the expression of FAT10, a gene counteracting the tumor suppressor p53.

Choi Yongwook Y Kim Jong Kyoung JK Yoo Joo-Yeon JY

Molecular oncology 20140124 3

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 ...[more]

PMID: 24518302

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