Different localization of Hsp105 family proteins in mammalian cells

Hsp105α and Hsp105β of the HSP105 family are alternatively spliced products derived from an hsp 105 gene transcript. Hsp105α is constitutively expressed and also induced by various stress, whereas Hsp105β, lacking 44 amino acids from Hsp105α, is specifically expressed during mild heat shock. Although Hsp105α is shown to localize in the cytoplasm of mammalian cells, cellular localization of Hsp105β is not known. In this study, we showed that Hsp105β localized in the nucleus of cells in contrast to cytoplasmic Hsp105α, suggesting that these proteins function in different cellular compartments of cells. Using deletion and substitution mutants of Hsp105α and Hsp105β, we revealed that these proteins had a functional nuclear localization signal (NLS) and a nuclear export signal (NES). Furthermore, Hsp105α accumulated in the nucleus of cells when treated with leptomycin B, a specific inhibitor of NES-dependent nuclear export. siRNA for importin β, an essential component for NLS-dependent nuclear transport, inhibited the nuclear localization of Hsp105β. Furthermore, the 44 amino acids sequence found in Hsp105α but not in Hsp105β suppressed the NLS activity. Thus, the different localization of Hsp105α and Hsp105β is suggested to be due to the suppressed NLS activity in Hsp105α.