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Hepatocyte homeostasis for chromosome ploidization and liver function is regulated by Ssu72 protein phosphatase
Author(s) -
Kim SeHyuk,
Jeon Yoon,
Kim HyunSoo,
Lee JinKwan,
Lim Han Jeong,
Kang Donglim,
Cho Hyeseong,
Park CheolKeun,
Lee Ho,
Lee ChangWoo
Publication year - 2016
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.28281
Subject(s) - biology , endoreduplication , hepatocyte , microbiology and biotechnology , liver injury , cell cycle , cancer research , cell , genetics , endocrinology , in vitro
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 knockout mouse model, 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 associated with impaired liver damage response and increased markers of liver injury and seemed to mimic the phenotypic features of liver diseases such as fibrosis, steatosis, and steatohepatitis. In addition, depletion of Ssu72 caused deregulation of cell cycle progression by overriding the restriction point of the cell cycle and aberrantly promoting DNA endoreplication through G 2 /M arrest. Conclusion : Ssu72 plays a substantial role in the maintenance of hepatic chromosome homeostasis and would allow monitoring of liver function. (H epatology 2016;63:247–259)