Ubiquitination rescues heat-shocked lcb1 cells from death.

Riezman/EMBO

Canonical heat shock proteins (Hsps) help fold proteins. So it is easy to presume that, when Hsps are compromised, heat shock does its damage by depleting the cell of functional, folded proteins. But now Sylvie Friant, Karsten Meier, and Howard Riezman (University of Geneva, Switzerland) find that it is the toxicity of the denatured proteins that is the death knell for severely heat shocked cells, and that destruction of the damaged proteins via ubiquitination can rescue the cell from death.

The ubiquitination connection arose when the group found the polyubiquitin gene UBI4 as a high copy suppressor of lcb1, a mutant in heat shock induction. UBI4 did not restore Hsp expression to the cells, but did reduce death and protein aggregation at high temperature and bring protein degradation and ubiquitination rates back to normal.

Where UBI4 succeeded, Hsps failed: Overexpression of Hsps did not rescue lcb1 at high temperature. Thus, although heat shock increases the demand for Hsp action, it is not this folding action but destruction by ubiquitination that keeps the cells alive. “Instead of refolding the proteins,” says Riezman, “the cells simply degrade them.” The cells then hang on until they can make newly synthesized and properly folded proteins. ▪

References:

Friant, S., et al.
2003
.
EMBO J.
22
:
3783
–3791.