Se-Hyuk Kim1, Yoon Jeon1,2, Hyun-Soo Kim1, Jin-Kwan Lee3, Han Jeong Lim2, Donglim Kang1, Hyeseong Cho4, Cheol-Keun Park5, Ho Lee2,* and Chang-Woo Lee1,3,*
1 Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea
2 Graduate School of Cancer Science and Policy, Research Institute, National Cancer Center, Goyang, Korea
3 Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea
4 Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon, Korea
5 Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
*Adress reprint requests to Chang-Woo Lee, Ph.D., Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea. , Ho Lee, Ph.D., Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, Korea.
Hepatocyte chromosome polyploidization is an important feature of liver development, and seems to be required for response to liver stress and injury signals. However, the question of how polyploidization can be tightly regulated in liver growth remains to be answered. Using a conditional knock-out mouse model, the liver-specific depletion of Ssu72 protein phosphatase was found to result in impairment in regulation of polyploidization. Interestingly, the aberrant polyploidization in Ssu72-depleted mice was found to be associated with impaired liver damage response and increased markers of liver injury, and also seemed to mimic the phenotypic features of liver diseases such as fibrosis, steatosis and steatohepatitis. In addition, the depletion of Ssu72 caused deregulation of cell cycle progression by overriding the restriction-point of cell cycle and aberrantly promoting DNA endoreplication via G2/M arrest. In conclusion, our results suggest that Ssu72 plays a substantial role in maintenance of hepatic chromosome homeostasis, and would allow monitoring of liver function. This article is protected by copyright. All rights reserved.
Keywords : Ssu72 phosphatase; chromosome ploidy; liver development; conditional knock-out mouse; non alcoholic fatty liver disease