title: Interaction of LHBs with C53 promotes hepatocyte mitotic entry: A novel             mechanism for HBV-induced hepatocellular carcinoma.
abstract: The pre-S mutant LHBs, especially the pre-S2 type, is believed to be crucial             in HBV-associated hepatocellular carcinogenesis. However, the mechanism of HBV-induced             hepatocellular carcinoma is not fully understood. To identify the mechanism, pre-S2             LHBs-interacting proteins were studied, by performing a yeast two-hybrid screen             of a human liver cDNA library. Screening of the library resulted in the isolation             of several positive clones. Sequencing of the positive clones identified the full-length             cDNA of the C53 gene. After identiﬁcation of the interaction, the roles of LHBs             on Cdk1, Chk1 activation and mitotic entry were studied. Screening of the library             resulted in the isolation of several positive clones, that encoded the full-length             cDNA of the C53 gene. We found that C53 interacts with pre-S2 LHBs both in vitro             and in vivo, but not with LHBs or other mutants. The binding of pre-S2 LHBs with             C53 causes increased Cdk1 activation and mitotic entry, and the function of Chk1             is partially inhibited by the binding of pre-S2 LHBs with C53. Taken together,             our results strongly suggest that the binding of pre-S2 LHBs with C53 is a novel             negative regulator of the checkpoint response. By counteracting C53, pre-S2 LHBs             promotes Cdk1 activation and mitotic entry in unperturbed cell cycle progression             and delays the function of Chk1, which may be a novel potential mechanism for             HBV-induced hepatocellular carcinoma (HCC).
authors.affiliation: Wound Healing and Cell Biology Laboratory, The First Affiliated Hospital, and Camital Medical University, Beijing 100853, PR China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Lei
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Yuying
authors.initials: Y
authors.lastname: Yang
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: Ren
authors.forename: Ben
authors.initials: B
authors.lastname: Li
authors.forename: Shunai
authors.initials: S
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Fu
authors.forename: Jinqian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D018797:Cell Cycle Proteins; D002472:Cell Transformation, Viral / Q000502:physiology*; D000071877:Checkpoint Kinase 1; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus; D006801:Humans; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D008938:Mitosis; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins; D020798:Two-Hybrid System Techniques
chemical_list: C405928:CDK5RAP3 protein, human; D018797:Cell Cycle Proteins; D006514:Hepatitis B Surface Antigens; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D025521:Tumor Suppressor Proteins; C050807:presurface protein 2, hepatitis B surface antigen; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; D016203:CDC2 Protein Kinase