APCCdh1controls cell cycle entry during liver regeneration.
Cdh1 is one of the two adaptor proteins of anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase controlling mitosis and DNA replication. To date, the in vivo functions of Cdh1 have not been fully explored. In order to characterize Cdh1 in liver regeneration, we generated a conditional knock-out mouse model. Our data showed that loss of Cdh1 leads to increased and extended S phase progression possibly due to the upregulation of cyclin D1. Moreover, the increased DNA replication resulted in activated DNA damage response. Interestingly, the final liver weight after partial hepatectomy in the Cdh1 depleted mice did not differ from that of the controls, implying that Cdh1 is not required for the competence of hepatocytes to regenerate itself.
Anhui Medical University, Hefei 230032, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China.
Ranran
R
Cheng
Anhui Medical University, Hefei 230032, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China.
Xin
X
Liang
Anhui Medical University, Hefei 230032, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China.
Quancheng
Q
Zhao
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China; National Center for Protein Sciences (Beijing), Beijing 102206, China.
Zhusheng
Z
Lian
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China; National Center for Protein Sciences (Beijing), Beijing 102206, China.
Lichun
L
Tang
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China; National Center for Protein Sciences (Beijing), Beijing 102206, China.
Chen
C
Qiu
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China; National Center for Protein Sciences (Beijing), Beijing 102206, China. Electronic address: chenhuan@smmu.edu.cn.
Huan
H
Chen
Anhui Medical University, Hefei 230032, China; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: pzhang@bcm.edu.
Pumin
P
Zhang
D000818:Animals; D064200:Cdh1 Proteins / Q000378:metabolism*; D002453:Cell Cycle; D016213:Cyclins / Q000378:metabolism; D004261:DNA Replication; D017353:Gene Deletion; D006498:Hepatectomy; D008115:Liver Regeneration; D018345:Mice, Knockout; D010641:Phenotype; D016196:S Phase; D013312:Stress, Physiological
D064200:Cdh1 Proteins; D016213:Cyclins
Cdh1; Liver regeneration; Replication