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Importin KPNA2, NBS1, DNA Repair and Tumorigenesis

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Abstract

During the past 20 years, the MRE11–RAD50–NBS1 complex has become an increasingly important focus in basic and clinical cancer research. One main conceptual step forward was made with the discovery of NBS1 and the understanding of its critical pathophysiological role in Nijmegen breakage syndrome. Major efforts were carried out to define the role in DNA repair of this complex. Recently, basic research has continuously extended our understanding of the complexity of the NBS1 complex. MRE11–RAD50–NBS1 complex can no longer be viewed as having a single role in DNA damage repair since it also serves as a sensor and a mediator in cell cycle checkpoint signaling. Meanwhile, studies have challenged the concept that NBS1 only functions as a tumor suppressor in preserving genome integrity in the nucleus. It may also provide an oncogenic role in the cytoplasm which is associated with the PI3-kinase/AKT-activation pathway. Consistent with this aspect, a growing body of clinical evidence suggests that NBS1 contains a deleterious character that depends on its subcellular localization. This review focuses on recent experimental evidences demonstrating how NBS1 is translocated into the nucleus by an importin KPNA2 which mediates NBS1 subcellular localization and the functions of the NBS1 complex in tumorigenesis.

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Acknowledgements

We thank Drs. P. Suresh and M.-K. Chern for their critical comments on the manuscript. We did not cite all of the excellent work that has been done in this field. We apologize to my colleagues who may feel that their work is underevaluated. This work was supported by National Health Research Institutes NHRI-EX94-9329SI (K.J.W.), NHRI-EX94-9328SI (S.C.T.), National Research Program for Genomic Medicine-Department of Health DOH94-TD-G-111-012 (K.J.W.), and National Science Council NSC 93-2320-B-002-38 (S.C.T.), NSC-94-2311-B-010-011 (K.J.W.).

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Authors and Affiliations

  1. Department of Microbiology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Jen-Ai Road, Taipei, 10063, Taiwan

    Shu-Chun Teng, Shun-Fu Tseng, Chui-Wei Wong & Li Kao

  2. Institute of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

    Shu-Chun Teng

  3. Institute of Biochemistry, National Yang-Ming University, Taipei, Taiwan

    Kou-Juey Wu

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  1. Shu-Chun Teng
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  2. Kou-Juey Wu
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Correspondence to Shu-Chun Teng.

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Teng, SC., Wu, KJ., Tseng, SF. et al. Importin KPNA2, NBS1, DNA Repair and Tumorigenesis. J Mol Hist 37, 293–299 (2006). https://doi.org/10.1007/s10735-006-9032-y

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