id="title" class="nomar"Nucleocytoplasmic Transport: a Target for Cellular Control
- Rockefeller University
- Institute for Systems Biology / Seattle Biomedical Research Institute
- University of Texas Southwestern Medical Center
- University of California San Francisco
Yuh Min Chook
The sole mediators of exchange between the nuclear and cytoplasmic compartments are nuclear pore complexes (NPCs), comprised of proteins termed nucleoporins or Nups. Nucleocytoplasmic transport is mostly driven by soluble transport factors termed karyopherins that carry their cognate cargos across the NPC. This transport is regulated at multiple levels, including cargo recognition by karyopherins and interactions with the NPC. The NPC also plays a key regulatory role in gene expression by influencing nuclear architecture and acting as a point of control for various nuclear processes. Major pathological cellular processes are associated with altered nucleocytoplasmic transport, and many viruses target components of the nucleocytoplasmic transport pathway to usurp it. Hence, nucleoporins and transport factors are key potential targets for drug therapy. But they have been almost entirely neglected so far, because only recently have we comprehensively inventoried both the transport factors and the molecular constituents of the NPC, and gained an understanding of critical parameters of NPC function and nucleocytoplasmic exchange. Here, we focus on two of the key regulatory areas of nucleocytoplasmic transport, where structural information is most likely to lead to fundamental mechanistic insights into these regulatory processes. This in turn will reveal candidate targets for intervention and control by small molecules, ultimately leading to useful probes of cellular function as well as drug discovery.