A Nuclear Localization Signal Is Essential for Stress-induced Dimer-to-Trimer Transition of Heat Shock Transcription Factor 3

Abstract

Expression of heat shock genes is regulated mainly at the level of transcription by heat shock transcription factors (HSFs). In avian, HSF1 and HSF3 are maintained in a cryptic monomer and dimer form, respectively, in the cytoplasm in the absence of stress. Upon heat stress, they undergo conformational change associated with the formation of a trimer and nuclear translocation. In this study, we identified regions that are necessary for the dimer-to-trimer transition of chicken HSF3 (cHSF3) upon stress conditions. One of these regions coincides with a functional nuclear localization signal (NLS) of cHSF3 that was recognized by a nuclear transport receptor importin alpha. Point mutations of basic amino acids in the NLS inhibit both nuclear translocation and trimer formation of cHSF3. These results demonstrate that the NLS acts positively on the trimer formation of cHSF3 upon stress conditions.