Anat Cell Biol.  2017 Jun;50(2):77-85. 10.5115/acb.2017.50.2.77.

The molecular mechanism for nuclear transport and its application

Affiliations
  • 1Department of Anatomy, Pusan National University School of Medicine, Yangsan, Korea. hedgehog@pusan.ac.kr
  • 2BEER, Busan Society of Evidence-Based mEdicine and Research, Busan, Korea.
  • 3Gene and Cell Therapy Research Center for Vessel-associated Diseases, Pusan National University, Yangsan, Korea.

Abstract

Transportation between the cytoplasm and the nucleoplasm is critical for many physiological and pathophysiological processes including gene expression, signal transduction, and oncogenesis. So, the molecular mechanism for the transportation needs to be studied not only to understand cell physiological processes but also to develop new diagnostic and therapeutic targets. Recent progress in the research of the nuclear transportation (import and export) via nuclear pore complex and four important factors affecting nuclear transport (nucleoporins, Ran, karyopherins, and nuclear localization signals/nuclear export signals) will be discussed. Moreover, the clinical significance of nuclear transport and its application will be reviewed. This review will provide some critical insight for the molecular design of therapeutics which need to be targeted inside the nucleus.

Keyword

Nuclear transport; Nucleoporins; Ran; Karyopherins; Nuclear localization signal

MeSH Terms

Active Transport, Cell Nucleus*
Carcinogenesis
Cell Physiological Processes
Cytoplasm
Gene Expression
Karyopherins
Nuclear Localization Signals
Nuclear Pore
Nuclear Pore Complex Proteins
Signal Transduction
Transportation
Karyopherins
Nuclear Localization Signals
Nuclear Pore Complex Proteins

Figure

  • Fig. 1 The nuclear transport cycle of proteins. (A) Import cycle for importin-αβ. (B) Import cycle for importin-β. (C) Export cycle. See main text for details. NLS, nuclear localization signal; NPC, nuclear pore complex; NES, nuclear export signal.

  • Fig. 2 Examples of NLSs and predictive location of NLSs. PY, proline-tyrosine; NLS, nuclear localization signal.

  • Fig. 3 3D structures of representative karyopherin-cargo complex. (A) Structure of importin-α with HIV-1 Tat NLS. (B) Structure of importin-β with RpL4 PY-NLS. (C) Structure of CRM1-Ran-RanBP1 with CPEB4 NES. Indicated number of amino acid residues are the binding sites of each karyopherins. These figures downloaded from RCSB PDB (http://www.rcsb.org/pdb/home/home.do). NLS, nuclear localization signal; PY, proline-tyrosine; NES, nuclear export signal.


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