Elsing et al. reveal how some vulnerable mitotic cells protect themselves from stress.

One way that cells cope with stress is by making heat-shock proteins such as Hsp70 that shield other proteins from damage. The transcription factor HSF1 serves as the main activator for heat-shock protein genes. During interphase, another transcription factor, HSF2, collaborates with HSF1 to switch on expression of heat-shock genes. During mitosis, however, cells become more susceptible to stress because they curtail this induction of heat-shock genes.

To their surprise, Elsing et al. found that HSF2 turns against its partner during mitosis. The researchers determined that stressed mitotic cells could still produce Hsp70 but only if HSF2 is absent. The team also discovered that the interaction between the two transcription factors changes. HSF2 obstructs HSF1’s access to chromatin during mitosis, possibly because HSF2 binds tightly to the promoter for the Hsp70 gene. HSF2’s actions also affect survival during stress. Compared with control cells, mitotic cells with low levels of HSF2 were more likely to live through a period of high temperatures and less likely to show defects in chromosome separation.

HSF2 therefore appears to increase mitotic cells’ vulnerability. But Elsing et al. found that several cell lines, including the HeLa tumor cell line, adapt by turning down HSF2 expression during mitosis, allowing them to produce Hsp70 and endure hardship. It’s still unclear why only some cell lines respond in this way, as researchers had thought that cells uniformly shut down gene transcription during mitosis. However, Elsing et al.’s results show that mitotic cells keep tight control on production of some proteins, such as Hsp70, in order to ensure their survival during mitosis.

References

References
Elsing
,
A.N.
, et al
.
2014
.
J. Cell Biol.
.

Author notes

Text by Mitch Leslie