We used a mutant strain of hsf-1 hsf-1 sy441 hsf-1 sy441thats a premature stop containsat eliminates the transactivation domain of HSF-1 and is likely to be a null mutant (Hajdu-Cronin et al., 2004).
For example, Hsp90, which under normal conditions is constitutively bound to HSF-1 to keep HSF-1 in an inactive state, might act as the sensor for subtle cytoskeletal disruptions and dissociate from HSF-1.
However, MGO induces the formation of Hsf-1 homodimers, followed by the formation of Hsf-1 homotrimers (Figure 5A), suggesting Hsf-1 activation.
Indeed, in this work we show that oligomerization of Hsf-1 is accompanied by a dramatic decrease in the interaction between Hsp90 and Hsf-1 (Figure 5G), highlighting the critical activation of Hsf-1 in response to MGO.
We hypothesize that HSF-1 and DAF-16 can interact within intestinal cells to optimize expression of HSF-1 and DAF-16 target genes that may extend lifespan.
Oligomerization and phosphorylation of Hsf-1, as well as gain of DNA binding activity, are all well described hallmarks for activation of Hsf-1 [36], [36].
An allele specific PCR using primers sy441F1, sy441F2 and sy441R1 was performed for hsf-1 genotyping.
In mammalian cells, induction of HSP70 requires activation and nuclear localization of HSF-1 [31], [31].
Hsp90-containing multichaperone complexes appear to be the most relevant repressors of Hsf-1 activity [37].
A similar mechanism is also likely to be involved in regulation of Hsf-1.
Hsf-1−/− cells revealed that the effect of 17-AAG on P23H aggregation was dependent on HSF-1, whereas the effect on R135L was HSF-1 independent.
