Overexpression of ABIN-2, a negative regulator of NF-{kappa}B, delays liver regeneration in the ABIN-2 transgenic mice

Journal Article · Fri Mar 31 04:00:00 EST 2006 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2006.01.114· OSTI ID:20798875

Li, C -C ^[1]; Chou, C -K ^[2]; Wang, M -H ^[3]; Tsai, T -F ^[4]

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1. Faculty of Life Sciences and Institute of Genetics, National Yang-Ming University, Taipei, Taiwan (China)
2. Department of Life Science, Chang Gung University, Taoyuan, Taiwan (China)
3. Laboratory Animal Center, Tzu-Chi University, Hualien, Taiwan (China)
4. Faculty of Life Sciences and Institute of Genetics, National Yang-Ming University, Taipei, Taiwan (China) and Department of Medical Research and Education, Taipei Veterans General Hospital, Taiwan (China) and Division of Molecular and Genomic Medicine, National Health Research Institute, Zhunan, Taiwan (China)

Activation of NF-{kappa}B 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-{kappa}B activation-2, ABIN-2, is an inhibitor of NF-{kappa}B. 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 8 h post-hepatectomy. To test that the inducible expression of ABIN-2 serves to regulate NF-{kappa}B 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-{kappa}B nuclear translocation, which peaked at around 2-4 h 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-{kappa}B activation during liver regeneration.

• OSTI ID: 20798875
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 342; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BIOLOGICAL REGENERATION
CELL CYCLE
HEPATECTOMY
LIVER
PROTEINS
TRANSGENIC MICE
TRANSLOCATION