techniques

as rass destruction. Ubiquitination entails a reaction cascade that transfers activated ubiquitin from a ubiquitin-activating and the lumen of the endoplasmic reticulum (ER). Review TRENDS in Cell Biology Vol.16 No.12enzyme (E1) to a family of ubiquitin-conjugating enzymes (E2). The E2s cooperate with the large group of ubiquitin ligases (E3) to modify target molecules covalently with ubiquitin [4]. Notably, stress induces expression of components of the ubiquitin pathway, demonstrating that protein folding and degradation are also linked at the transcriptional level. The step that determines if a deviant protein is refolded or degraded is termed ‘molecular triage ’ [5]. Protein Sensing stress in the cytosol The cytosolic stress sensor is the heat-shock transcription factor 1 (HSF1) [10]. In yeast, HSF1 regulates nearly 3 % of the genomic loci [11]. The main targets of HSF1 are chaperones of the Hsp70 and Hsp90 family and chaper-onins. In the absence of misfolded proteins, chaperones bind HSF1 to keep it inactive. When these chaperones engage in the repair of damaged proteins, HSF1 is liber-ated and initiates the transcription of stress-responsive genes. Originally, it was thought that intramolecular interactions between HSF1 molecules lead to the forma-tion of a HSF1 homotrimer, which constitutes the activ