THE STRESS-RESPONSE TO LOSS OF SIGNAL RECOGNITION PARTICLE FUNCTION IN SACCHAROMYCES-CEREVISIAE

It has been shown previously that growth and endoplasmic reticulum (ER ) translocation defects occur in response to depletion of the 54-kDa s ubunit of signal recognition particle (SRP54) in Saccharomyces cerevis iae (Hann, B. B., and Waiter, P. (1991) Cell 67, 131-144). We report h ere that cells depleted of SRP54p undergo a general stress response, t he onset of which is observed almost two-cell doublings after SRP54 pr otein levels fall below the limits of detection. The stress response t o SRP54p depletion occurs in two distinct phases, unlike the response to other stressors such as heat shock. In the initial phase, the cytop lasmic Hsp70 levels are drastically increased coincident with an abrup t slowing of growth and accumulation of untranslocated species of the ER-resident chaperone BiP. During this first response, levels of the y east DnaJ homolog Ydj1p are also increased. In the second phase, which is detected 5 h later, levels of the cytoplasmic heat shock proteins Hsp82 and Hsp104 are increased. BiP is also induced during this second phase, while the ER levels of the resident foldase protein disulfide isomerase are significantly reduced. Since only those cytoplasmic stre ss proteins which have been shown to participate in membrane transloca tion are induced in the first phase, these findings indicate the prese nce of a stress response specific to accumulation of secretory protein precursors in the cytoplasm.