shock response (HSR) pathway in humans by acting as the major transcription factor for heat shock proteins. The HSR plays a protective role by ensuring proper folding and distribution of proteins within cells. This pathway is induced by not only temperature stress, but also by a variety of other stressors such as hypoxic conditions and exposure to contaminants. HSF1 transactivates genes for many cytoprotective proteins involved in heat shock, DNA damage repair, and metabolism. This illustrates the versatile role of HSF1 in not only the heat shock response, but also in aging and diseases. Mechanism of action Under non-stress conditions, HSF1 exists primarily as an inactive monomer located throughout the nucleus and the cytoplasm. In its monomeric form, HSF1 activation is repressed by interaction with chaperones such as heat shock proteins Hsp70 and Hsp90, and TRiC/CCT. In the event of proteotoxic stress such as heat shock, these chaperones are released from HSF1 to perform their protein-folding roles; simultaneously, the export of HSF1 to the cytoplasm is inhibited. These actions allow HSF1 to trimerize and accumulate in the nucleus to stimulate transcription of target genes. Clinical significance HSF1 is a promising drug target in cancer and proteopathy. The genes activated by HSF1 under heat shock conditions have been recently shown to differ from those activated in malignant cancer cells, and this cancer-specific HSF1 panel of genes has indicated poor prognosis in breast cancer. The ability of cancer cells to use HSF1 in a unique manner gives this protein significant clinical implications for therapies and prognoses. In the case of protein-folding diseases such as Huntington's disease (HD), however, induction of the heat shock response pathway would prove beneficial. In recent years, using cells that express the poly-glutamine expansion found in HD, it has been shown that both the HSR and HSF1 levels are reduced after heat shock. This reduced ability of diseased cells to respond to stress helps to explain the toxicity associated with certain diseases. Interactions HSF1 has been shown to interact with: CEBPB, HSF2, HSPA1A, HSPA4, Heat shock protein 90kDa alpha (cytosolic) member A1, NCOA6, RALBP1 and SYMPK. See also Heat shock factor Heat shock protein Transcription factor References Further reading External links Transcription factors