Overexpression of ABIN-2, a negative regulator of NF-kappaB, delays liver regeneration in the ABIN-2 transgenic mice.
Activation of NF-kappaB is one of the earliest responses at the start of liver regeneration, and is required for hepatocyte cell cycle progression. The A20-binding inhibitor of NF-kappaB activation-2, ABIN-2, is an inhibitor of NF-kappaB. However, its effects on hepatocyte cell cycle progression are not known and its involvement in liver regeneration has not been explored. In this study, the temporal expression pattern of the mouse ABIN-2 was studied during liver regeneration induced by partial hepatectomy. We demonstrate that ABIN-2 is rapidly and transiently induced, and expression peaked at around 8h post-hepatectomy. To test that the inducible expression of ABIN-2 serves to regulate NF-kappaB during liver regeneration, transgenic mice overexpressing human ABIN-2 protein in the liver were generated. Our transgenic data demonstrated that overexpression of ABIN-2 inhibited NF-kappaB nuclear translocation, which peaked at around 2-4h post-hepatectomy, and this led to an impairment of the G1/S transition as well as a delay in hepatocyte cell cycle progression of the regenerating liver. In addition, overexpression of ABIN-2 specifically inhibited endogenous ABIN-2 mRNA induction, suggesting a negative feedback mechanism for ABIN-2 expression. In conclusion, ABIN-2 may function as a negative regulator that downregulates NF-kappaB activation during liver regeneration.
Li
Chao-Chin
CC
Faculty of Life Sciences and Institute of Genetics, National Yang-Ming University, Taipei, Taiwan.
Chou
Chen-Kung
CK
Wang
Ming-Hseng
MH
Tsai
Ting-Fen
TF
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D005786:Gene Expression Regulation; D006498:Hepatectomy; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors
D048868:Adaptor Proteins, Signal Transducing; D016328:NF-kappa B; D021122:Protein Subunits; D012333:RNA, Messenger; C434062:TNIP2 protein, human; C503281:Tnip2 protein, mouse; D004247:DNA