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Forkhead box class O transcription factors in liver function and disease
Author(s) -
Tikhanovich Irina,
Cox Josiah,
Weinman Steven A.
Publication year - 2013
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12021
Subject(s) - foxo3 , foxo1 , transcription factor , forkhead transcription factors , autophagy , keap1 , transcriptional regulation , foxm1 , biology , microbiology and biotechnology , regulator , gluconeogenesis , transcription (linguistics) , cancer research , medicine , apoptosis , endocrinology , gene , genetics , metabolism , linguistics , philosophy
The forkhead box transcription factor class O ( FOXO ) family represents a group of transcription factors that is required for a number of stress‐related transcriptional programs including antioxidant response, gluconeogenesis, cell cycle control, apoptosis, and autophagy. The liver utilizes several FOXO ‐dependent pathways to adapt to its routine cycles of feeding and fasting and to respond to the stresses induced by disease. FOXO 1 is a direct transcriptional regulator of gluconeogenesis, reciprocally regulated by insulin, and has profound effects on hepatic lipid metabolism. FOXO 3 is required for antioxidant responses and autophagy and is altered in hepatitis C infection and fatty liver. Emerging evidence suggests dysregulation of FOXO 3 in some hepatocellular carcinomas. FOXO s are notable for the extensive number of functionally significant posttranslational modifications that they undergo. Recent advances in our understanding how FOXO s are regulated are providing a more detailed picture of how specific combinations of posttranslational modifications alter both nuclear translocation as well as transcriptional specificity under different conditions. This review summarizes emerging knowledge of FOXO function in the liver, FOXO changes in liver disease, and the posttranslational modifications responsible for these effects.