TY - JOUR
T1 - Roles of the heat shock transcription factors in regulation of the heat shock response and beyond
AU - Pirkkala, L
AU - Nykänen, P
AU - Sistonen, L
PY - 2001/5
Y1 - 2001/5
N2 - The heat shock response, characterized by increased expression of heat shock proteins (Hsps) is induced by exposure of cells and tissues to extreme conditions that cause acute or chronic stress. Hsps function as molecular chaperones in regulating cellular homeostasis and promoting survival. If the stress is too severe, a signal that leads to programmed cell death, apoptosis, is activated, thereby providing a finely tuned balance between survival and death. In addition to extracellular stimuli, several nonstressful conditions induce Hsps during normal cellular growth and development. The enhanced heat shock gene expression in response to various stimuli is regulated by heat shock transcription factors (HSFs). After the discovery of the family of HSFs (i.e., murine and human HSF1, 2, and 4 and a unique avian HSF3), the functional relevance of distinct HSFs is now emerging. HSF1, an HSF prototype, and HSF3 are responsible for heat-induced Hsp expression, whereas HSF2 is refractory to classical stressors. HSF4 is expressed in a tissue-specific manner; similar to HSF1 and HSF2, alternatively spliced isoforms add further complexity to its regulation. Recently developed powerful genetic models have provided evidence for both cooperative and specific functions of HSFs that expand beyond the heat shock response. Certain specialized functions of HSFs may even include regulation of novel target genes in response to distinct stimuli.
AB - The heat shock response, characterized by increased expression of heat shock proteins (Hsps) is induced by exposure of cells and tissues to extreme conditions that cause acute or chronic stress. Hsps function as molecular chaperones in regulating cellular homeostasis and promoting survival. If the stress is too severe, a signal that leads to programmed cell death, apoptosis, is activated, thereby providing a finely tuned balance between survival and death. In addition to extracellular stimuli, several nonstressful conditions induce Hsps during normal cellular growth and development. The enhanced heat shock gene expression in response to various stimuli is regulated by heat shock transcription factors (HSFs). After the discovery of the family of HSFs (i.e., murine and human HSF1, 2, and 4 and a unique avian HSF3), the functional relevance of distinct HSFs is now emerging. HSF1, an HSF prototype, and HSF3 are responsible for heat-induced Hsp expression, whereas HSF2 is refractory to classical stressors. HSF4 is expressed in a tissue-specific manner; similar to HSF1 and HSF2, alternatively spliced isoforms add further complexity to its regulation. Recently developed powerful genetic models have provided evidence for both cooperative and specific functions of HSFs that expand beyond the heat shock response. Certain specialized functions of HSFs may even include regulation of novel target genes in response to distinct stimuli.
KW - Amino Acid Sequence
KW - Animals
KW - Heat-Shock Proteins/chemistry
KW - Heat-Shock Response/physiology
KW - Humans
KW - Molecular Sequence Data
KW - Phylogeny
KW - Protein Isoforms/physiology
KW - Sequence Alignment
KW - Transcription Factors/chemistry
U2 - 10.1096/fj00-0294rev
DO - 10.1096/fj00-0294rev
M3 - Review Article or Literature Review
C2 - 11344080
SN - 0892-6638
VL - 15
SP - 1118
EP - 1131
JO - FASEB Journal
JF - FASEB Journal
IS - 7
ER -