Fig. 7

Model of the response to misfolded myosin. Under normal conditions chaperones such as Hsp40, Hsp90 and Hsp70 sequester Hsf1 monomers (1) [83] in the cytoplasm. Upon accumulation of unfolded myosin in unc45b, smyd1b and hsp90a mutants, the chaperones bind to the misfolded myosin and release Hsf1 (2, 4). Remaining unfolded myosin is sent to the proteasome (5). Hsf1 monomers then form active homotrimers (3) which bind to HSEs in target genes (6), such as those of unc45b, hsp90a and myod. More than 1400 genes activated in the misfolded myosin response include those encoding TFs that indirectly activate downstream gene programs and thereby further diversify the response of the transcriptome