Interaction of LHBs with C53 promotes hepatocyte mitotic entry: A novel mechanism for HBV-induced hepatocellular carcinoma

  • Authors:
    • Yonghong Lei
    • Hao Liu
    • Yuying Yang
    • Xiaojie Wang
    • Na Ren
    • Ben Li
    • Shunai Liu
    • Jun Cheng
    • Xiaobing Fu
    • Jinqian Zhang
  • View Affiliations

  • Published online on: October 4, 2011     https://doi.org/10.3892/or.2011.1489
  • Pages: 151-159
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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).

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January 2012
Volume 27 Issue 1

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Spandidos Publications style
Lei Y, Liu H, Yang Y, Wang X, Ren N, Li B, Liu S, Cheng J, Fu X, Zhang J, Zhang J, et al: Interaction of LHBs with C53 promotes hepatocyte mitotic entry: A novel mechanism for HBV-induced hepatocellular carcinoma. Oncol Rep 27: 151-159, 2012
APA
Lei, Y., Liu, H., Yang, Y., Wang, X., Ren, N., Li, B. ... Zhang, J. (2012). Interaction of LHBs with C53 promotes hepatocyte mitotic entry: A novel mechanism for HBV-induced hepatocellular carcinoma. Oncology Reports, 27, 151-159. https://doi.org/10.3892/or.2011.1489
MLA
Lei, Y., Liu, H., Yang, Y., Wang, X., Ren, N., Li, B., Liu, S., Cheng, J., Fu, X., Zhang, J."Interaction of LHBs with C53 promotes hepatocyte mitotic entry: A novel mechanism for HBV-induced hepatocellular carcinoma". Oncology Reports 27.1 (2012): 151-159.
Chicago
Lei, Y., Liu, H., Yang, Y., Wang, X., Ren, N., Li, B., Liu, S., Cheng, J., Fu, X., Zhang, J."Interaction of LHBs with C53 promotes hepatocyte mitotic entry: A novel mechanism for HBV-induced hepatocellular carcinoma". Oncology Reports 27, no. 1 (2012): 151-159. https://doi.org/10.3892/or.2011.1489