TY - JOUR
T1 - Expression of HSF2 decreases in mitosis to enable stress-inducible transcription and cell survival
AU - Elsing, Alexandra N.
AU - Aspelin, Camilla
AU - Björk, Johanna K.
AU - Bergman, Heidi A.
AU - Himanen, Samu V.
AU - Kallio, Marko
AU - Roos-Mattjus, Pia
AU - Sistonen, Lea
PY - 2014
Y1 - 2014
N2 - Unless mitigated, external and physiological stresses are
detrimental for cells, especially in mitosis, resulting
in chromosomal missegregation, aneuploidy, or apoptosis.
Heat shock proteins (Hsps) maintain protein homeostasis
and promote cell survival. Hsps are transcriptionally
regulated by heat shock factors (HSFs). Of these, HSF1 is
the master regulator and HSF2 modulates Hsp expression by
interacting with HSF1. Due to global inhibition of
transcription in mitosis, including HSF1-mediated
expression of Hsps, mitotic cells are highly vulnerable
to stress. Here, we show that cells can counteract
transcriptional silencing and protect themselves against
proteotoxicity in mitosis. We found that the condensed
chromatin of HSF2-deficient cells is accessible for HSF1
and RNA polymerase II, allowing stress-inducible Hsp
expression. Consequently, HSF2-deficient cells exposed to
acute stress display diminished mitotic errors and have a
survival advantage. We also show that HSF2 expression
declines during mitosis in several but not all human cell
lines, which corresponds to the Hsp70 induction and
protection against stress-induced mitotic abnormalities
and apoptosis
AB - Unless mitigated, external and physiological stresses are
detrimental for cells, especially in mitosis, resulting
in chromosomal missegregation, aneuploidy, or apoptosis.
Heat shock proteins (Hsps) maintain protein homeostasis
and promote cell survival. Hsps are transcriptionally
regulated by heat shock factors (HSFs). Of these, HSF1 is
the master regulator and HSF2 modulates Hsp expression by
interacting with HSF1. Due to global inhibition of
transcription in mitosis, including HSF1-mediated
expression of Hsps, mitotic cells are highly vulnerable
to stress. Here, we show that cells can counteract
transcriptional silencing and protect themselves against
proteotoxicity in mitosis. We found that the condensed
chromatin of HSF2-deficient cells is accessible for HSF1
and RNA polymerase II, allowing stress-inducible Hsp
expression. Consequently, HSF2-deficient cells exposed to
acute stress display diminished mitotic errors and have a
survival advantage. We also show that HSF2 expression
declines during mitosis in several but not all human cell
lines, which corresponds to the Hsp70 induction and
protection against stress-induced mitotic abnormalities
and apoptosis
U2 - 10.1083/jcb.201402002
DO - 10.1083/jcb.201402002
M3 - Article
VL - 206
SP - 735
EP - 749
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 6
ER -