Differential regulation of HSP27 oligomerization in tumor cells grown in vitro and in vivo

Bruey, Jean‐Marie; Paul, Catherine; Fromentin, Annie; Hilpert, Sophie; Arrigo, André‐Patrick; Solary, Éric; Garrido, Carmen

doi:10.1038/sj.onc.1203850

Cited by 132 publications

(124 citation statements)

References 38 publications

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“…Accordingly, gel filtration experiments showed that an HSP27 mutant in which the three phosphorylable serines have been replaced by alanines (HSP27-Ala) abundantly yields large oligomers, whereas an HSP27 mutant in which the serine residues have been replaced by the phosphomimetic aspartates (HSP27-Asp) exclusively yields small oligomers (Lambert et al, 1999;Bruey et al, 2000;Parcellier et al, 2006) ( Figure 2d). For these studies we used colon cancer REG cells stably transfected with the different HSP27 mutants because these cells do not express any detectable level of endogenous HSP27 (Bruey et al, 2000) ( Figure 2d). Using the same experimental conditions as in Figure 1, we found that although the HSP27-Ala mutant favoured overall SUMO-2/3 protein modification more efficiently than HSP27-wt, .…”

Section: Hsp27 Increases General Protein Sumoylation In Cellsmentioning

confidence: 99%

“…Clinical and experimental studies have showed that a constitutive accumulation of inducible HSPs (mainly HSP27 or HSP70) is associated with a poor prognosis and an increase in the tumorigenic and metastatic potential of tumour cells (Jaattela, 1995;Garrido et al, 1998;Bruey et al, 2000;Gurbuxani et al, 2001;Westerheide et al, 2006;Didelot et al, 2007). It would be interesting to determine whether defaults in the modulation of HSF1 sumoylation by HSP27 are involved in this abnormally high HSPs expression characteristic of cancer cells.…”

Section: Hsp27 Facilitates Hsf1 Sumoylationmentioning

confidence: 99%

“…The different activities of HSP27 seem to be modulated by the oligomerization pattern of the chaperone. We have shown, in vitro and in vivo, that large non-phosphorylated oligomers of HSP27 are responsible for the caspase-dependent antiapoptotic effect of this chaperone (Bruey et al, 2000). Other groups have shown that large oligomers are needed for HSP27 antioxidant activity (Rogalla et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Heat shock protein 27 is involved in SUMO-2/3 modification of heat shock factor 1 and thereby modulates the transcription factor activity

et al. 2009

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Heat shock protein 27 (HSP27) accumulates in stressed cells and helps them to survive adverse conditions. We have already shown that HSP27 has a function in the ubiquitination process that is modulated by its oligomerization/phosphorylation status. Here, we show that HSP27 is also involved in protein sumoylation, a ubiquitinationrelated process. HSP27 increases the number of cell proteins modified by small ubiquitin-like modifier (SUMO)-2/3 but this effect shows some selectivity as it neither affects all proteins nor concerns SUMO-1. Moreover, no such alteration in SUMO-2/3 conjugation is achievable by another HSP, such as HSP70. Heat shock factor 1 (HSF1), a transcription factor responsible for HSP expression, is one of the targets of HSP27. In stressed cells, HSP27 enters the nucleus and, in the form of large oligomers, binds to HSF1 and induces its modification by SUMO-2/3 on lysine 298. HSP27-induced HSF1 modification by SUMO-2/3 takes place downstream of the transcription factor phosphorylation on S303 and S307 and does not affect its DNA-binding ability. In contrast, this modification blocks HSF1 transactivation capacity. These data show that HSP27 exerts a feedback inhibition of HSF1 transactivation and enlighten the strictly regulated interplay between HSPs and HSF1. As we also show that HSP27 binds to the SUMO-E2-conjugating enzyme, Ubc9, our study raises the possibility that HSP27 may act as a SUMO-E3 ligase specific for SUMO-2/3.

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Section: Hsp27 Increases General Protein Sumoylation In Cellsmentioning

confidence: 99%

Section: Hsp27 Facilitates Hsf1 Sumoylationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Heat shock protein 27 is involved in SUMO-2/3 modification of heat shock factor 1 and thereby modulates the transcription factor activity

et al. 2009

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“…The protection induced by Hsp27 is highly correlated with its biochemical state (Bruey et al, 2000b). To determine whether PAs could modify the properties of Hsp27, we first analyzed the oxidative stress-induced dimerization of the protein in non-reducing polyacrylamide gel electrophoresis ( Figure 4a).…”

Section: Aptamers Modify the Biochemical Properties Of Hsp27mentioning

confidence: 99%

Inhibition of heat shock protein 27 (HspB1) tumorigenic functions by peptide aptamers

et al. 2011

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“…As cited above, HSP27 exhibits an antiapoptotic function, although this function is unlikely to account for the wtBRCA1-mediated resistance to heat stress. In response to various stresses, it has been found that HSP27 becomes phosphorylated and aggregates into supramolecular structures of up to several megadaltons (Benndorf et al, 1994;Bruey et al, 2000). Recently, several studies have documented that ectopic overexpression of HSP27 and several related proteins-a Bcrystallin (a small HSP of the vertebrate lens) and hspA (a small HSP of cyanobacteria)-rendered the host cells thermotolerant or resistant to hyperthermia (Aoyama et al, 1993;Trautinger et al, 1997;Nakamoto et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Role of BRCA1 in heat shock response

et al. 2003

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The heat shock response is an evolutionarily conserved response to heat and other stresses that promotes the maintenance of key metabolic functions and cell survival. We report that exposure of human prostate (DU-145) and breast (MCF-7) cancer cells to heat (421C) caused a rapid disappearance of the breast cancer susceptibility gene-1 (BRCA1) protein, starting at E1 h after the onset of heating and slightly lagging behind the increase in heat shock protein 70 (HSP70) levels. The heat-induced loss of BRCA1 occurred at the protein level, since: (1) BRCA1 mRNA expression was unaffected; and (2) the BRCA1 protein loss was also observed in DU-145 cells that expressed exogenous wild-type BRCA1 (wtBRCA1). In addition to heat regulation of BRCA1 protein levels, we also found that BRCA1 could modulate the heat shock response. Thus, wtBRCA1 overexpressing DU-145 cell clones showed significantly decreased sensitivity to heatinduced cytotoxicity; and Brca1 mutant mouse embryo fibroblasts showed increased sensitivity to heat. The DU-145 wtBRCA1 clones also showed increased expression of the small heat shock protein HSP27; and reporter assays revealed that wtBRCA1 stimulated a two to four-fold increase in HSP27 promoter activity, consistent with its ability to upregulate HSP27 mRNA and protein levels. In studies using epitope-tagged truncated BRCA1 proteins, the ability to stimulate the HSP27 promoter and to mediate heat-induced degradation required the aminoterminus but not the carboxyl-terminus of BRCA1. Although the heat-induced loss of BRCA1 appeared to be due to protein degradation, various protein metabolic agents (or combinations) failed to block this event, including: MG132 (a 26S proteasomal inhibitor), Nacetyl-leucyl-leucyl-norleucinal (a calpain inhibitor), z-VAD-fmk (a pan-caspase inhibitor), and ammonium chloride and chloroquine (which stabilize lysosomes). These findings suggest that in addition to its other functions, BRCA1 may participate in mammalian heat shock response pathways.

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Differential regulation of HSP27 oligomerization in tumor cells grown in vitro and in vivo

Cited by 132 publications

References 38 publications

Heat shock protein 27 is involved in SUMO-2/3 modification of heat shock factor 1 and thereby modulates the transcription factor activity

Heat shock protein 27 is involved in SUMO-2/3 modification of heat shock factor 1 and thereby modulates the transcription factor activity

Inhibition of heat shock protein 27 (HspB1) tumorigenic functions by peptide aptamers

Role of BRCA1 in heat shock response

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