Heat shock factor function and regulation in response to cellular stress, growth, and differentiation signals - PubMed (original) (raw)

Review

Heat shock factor function and regulation in response to cellular stress, growth, and differentiation signals

K A Morano et al. Gene Expr. 1999.

Abstract

Heat shock factors (HSF) activate the transcription of genes encoding products required for protein folding, processing, targeting, degradation, and function. Although HSFs have been extensively studied with respect to their role in thermotolerance and the activation of gene expression in response to environmental stress, the involvement of HSFs in response to stresses associated with cell growth and differentiation, and in response to normal physiological processes is becoming increasingly clear. In this work, we review recent advances toward understanding how cells transmit growth control and developmental signals, and interdigitate cellular physiology, to regulate HSF function.

PubMed Disclaimer

Figures

FIG. 1

FIG. 1

Conserved domain architecture of heat shock transcription factors. Critical regions of HSF are depicted with approximate relative locations in the different HSF molecules. Graphic representations are as follows: rounded rectangle, transcriptional activation domain (NTA, CTA); rectangle, DNA binding domain (DBD); star, leucine zipper motif oligomerization domain (OLIGO); circle, repression domain (REP). For simplicity, only HSF1 and HSF2 are shown from humans.

FIG. 2

FIG. 2

Cellular regulation of HSF. The inactive, monomeric form (left), and the transcriptionally active, trimerized HSF (right), are depicted along with signals and protein effectors responsible for regulation (see text for details). Serine residues that lie within the repression domain at positions 303 and 307, as numbered in human HSF, are depicted in their phosphorylated state in the inactive HSF molecule to reflect the negative role of phosphorylation in HSF regulation. Leucine zipper 4, found immediately proximal to the transcriptional activation region, is shown engaged in an intramolecular bridge thought to restrain HSF activity.

FIG. 3

FIG. 3

The Hsp90 chaperone complex in yeast. The subunits of the Hsp90 chaperone complex as found in yeast are depicted together, although it should be noted that composition of the complex is dynamic and involves the sequential binding and release of these co-chaperones. Two classes of protein have been shown to require the Hsp90 complex to function, protein kinases and transcription factors, and representatives of these classes with experimental evidence for interaction from the yeast system are shown [Cdc28 (31); weel (3); Mps1 (70); Ste11 (50); v-src (88); Hap1 (91); HSF (24, 60); steroid receptors (63)].

FIG. 4

FIG. 4

Cell cycle arrest of an HSF truncation mutant (A) HSF(1-583) cells arrest in a late stage of the cell cycle. HSF(1-583) cells grown at 30°C or shifted to the nonpermissive growth temperature of 37°C for 6 h were stained with DAPI to visualize the nucleus with epifluorescence microscopy (bar, 10 μm). Note the large daughter buds in cells grown at 37°C relative to those at the preshift condition. In addition, the nucleus has failed to migrate to the bud neck in these cells for initiation of mitotic separation. (B) The cell cycle in yeast.

References

    1. Abravaya K.; Myers M. P.; Murphy S. P.; Morimoto R. I. The human heat shock protein hsp70 interacts with HSF, the transcription factor that regulates heat shock gene expression. Genes Dev. 6:1153–1164; 1992. - PubMed
    1. Ali A.; Bharadwaj S.; O’Carroll R.; Ovsenek N. HSP90 interacts with and regulates the activity of heat shock factor 1 in Xenopus oocytes. Mol. Cell. Biol. 18:4949–4960; 1998. - PMC - PubMed
    1. Aligue R.; Akhavan-Niak H.; Russell P. A role for Hsp90 in cell cycle control: Weel tyrosine kinase activity requires interaction with Hsp90. EMBO J. 13:6099–6106; 1994. - PMC - PubMed
    1. Allen J. W.; Dix D. J.; Collins B. W.; Merrick B. A.; He C.; Selkirk J. K.; Poorman-Allen P.; Dresser M. E.; Eddy E. M. HSP70-2 is part of the synaptone-mal complex in mouse and hamster spermatocytes. Chromosoma 104:414–421; 1996. - PubMed
    1. Allen R. L.; O’Brien D. A.; Eddy E. M. A novel hsp70-like protein (P70) is present in mouse spermatogenic cells. Mol. Cell. Biol. 8:828–832; 1988. - PMC - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources