Regulation of tumor suppressors by nuclear-cytoplasmic shuttling.

Tumor suppressor proteins control the proliferation and survival of normal cells; consequently, their inactivation by gene mutations can initiate or drive cancer progression. Most tumor suppressors have been identified by genetic screening, and in many cases their function and regulation are poorly understood. Ten such proteins were recently shown to contain nuclear transport signals that facilitate their "shuttling" between the nucleus and cytoplasm. This type of dynamic intracellular movement not only regulates protein localization, but also often impacts on function. Here, we review the pathways by which tumor suppressors such as APC, p53, VHL, and BRCA1 cross the nuclear envelope and the impact of regulated nuclear import/export on protein function.