Expression of APOBEC2 is transcriptionally regulated by NF-kappaB in human hepatocytes.
Apolipoprotein B mRNA-editing enzyme catalytic subunit 2 (APOBEC2) is a member of the nucleic-acid-editing enzymes. However, the physiological function of APOBEC2 remains unclear. We demonstrate that APOBEC2 expression is strongly enhanced in response to both tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta. Inhibition of NF-kappaB activation invariably blocks TNF-alpha-induced APOBEC2 expression. The promoter region of APOBEC2 contains functional NF-kappaB response elements in the 5' untranslated region of the gene at -625/-616. These results show that APOBEC2 expression is regulated by pro-inflammatory cytokines via NF-kappaB activation and suggest a possible role of APOBEC2 in the pathophysiology of hepatic inflammation.
Matsumoto
Tomonori
T
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Shogoin, Kyoto 606-8507, Japan.
Marusawa
Hiroyuki
H
Endo
Yoko
Y
Ueda
Yoshihide
Y
Matsumoto
Yuko
Y
Chiba
Tsutomu
T
D000071478:APOBEC Deaminases; D045744:Cell Line, Tumor; D003564:Cytidine Deaminase / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006505:Hepatitis / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D022781:Hepatocytes / Q000201:enzymology*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*; D017393:RNA Editing / Q000187:drug effects / Q000235:genetics; D020218:Response Elements / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D007375:Interleukin-1; D009124:Muscle Proteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000071478:APOBEC Deaminases; C120388:APOBEC2 protein, human; D003564:Cytidine Deaminase