Intranuclear targeted delivery of functional NF-kappa B by 70 kDa heat shock protein

The 70 kDa heat shock protein (Hsp70) is a highly conserved, ubiquitous pro tein involved in chaperoning proteins to various cellular organelles. Here we show that when added exogenously to cells, Hsp70 is readily imported int o both cytoplasmic and nuclear compartments in a cell-type-specific fashion . We exploited this ability of Hsp70 to deliver NF-kappa B, a key transcrip tional regulator of inflammatory responses. We demonstrate that a fusion pr otein composed of a C-terminal Hsp70 peptide and the p50 subunit of NF-kapp a B was directed into the nucleus of cells, could bind DNA specifically, an d activated Ig kappa expression and TNF alpha production. We therefore prop ose that Hsp70 can be used as a vehicle for intracytoplasmic and intranucle ar delivery of proteins or DNA to modulate gene expression and thereby cont rol immune responses.