Translational Thermotolerance Provided by Small Heat Shock Proteins Is Limited to Cap-dependent Initiation and Inhibited by 2-Aminopurine

Abstract

Heat shock results in inhibition of general protein synthesis. In thermotolerant cells, protein synthesis is still rapidly inhibited by heat stress, but protein synthesis recovers faster than in naive heat-shocked cells, a phenomenon known as translational thermotolerance. Here we investigate the effect of overexpressing a single heat shock protein on cap-dependent and cap-independent initiation of translation during recovery from a heat shock. When overexpressing αB-crystallin or Hsp27, cap-dependent initiation of translation was protected but no effect was seen on cap-independent initiation of translation. When Hsp70 was overexpressed however, both cap-dependent and -independent translation were protected. This finding indicates a difference in the mechanism of protection mediated by small or large heat shock proteins. Phosphorylation of αB-crystallin and Hsp27 is known to significantly decrease their chaperone activity; therefore, we tested phosphorylation mutants of these proteins in this system. αB-crystallin needs to be in its non-phosphorylated state to give protection, whereas phosphorylated Hsp27 is more potent in protection than the unphosphorylatable form. This indicates that chaperone activity is not a prerequisite for protection of translation by small heat shock proteins after heat shock. Furthermore, we show that in the presence of 2-aminopurine, an inhibitor of kinases, among which is double-stranded RNA-activated kinase, the protective effect of overexpressing αB-crystallin is abolished. The synthesis of the endogenous Hsps induced by the heat shock to test for thermotolerance is also blocked by 2-aminopurine. Most likely the protective effect of αB-crystallin requires synthesis of the endogenous heat shock proteins. Translational thermotolerance would then be a co-operative effect of different heat shock proteins. Heat shock results in inhibition of general protein synthesis. In thermotolerant cells, protein synthesis is still rapidly inhibited by heat stress, but protein synthesis recovers faster than in naive heat-shocked cells, a phenomenon known as translational thermotolerance. Here we investigate the effect of overexpressing a single heat shock protein on cap-dependent and cap-independent initiation of translation during recovery from a heat shock. When overexpressing αB-crystallin or Hsp27, cap-dependent initiation of translation was protected but no effect was seen on cap-independent initiation of translation. When Hsp70 was overexpressed however, both cap-dependent and -independent translation were protected. This finding indicates a difference in the mechanism of protection mediated by small or large heat shock proteins. Phosphorylation of αB-crystallin and Hsp27 is known to significantly decrease their chaperone activity; therefore, we tested phosphorylation mutants of these proteins in this system. αB-crystallin needs to be in its non-phosphorylated state to give protection, whereas phosphorylated Hsp27 is more potent in protection than the unphosphorylatable form. This indicates that chaperone activity is not a prerequisite for protection of translation by small heat shock proteins after heat shock. Furthermore, we show that in the presence of 2-aminopurine, an inhibitor of kinases, among which is double-stranded RNA-activated kinase, the protective effect of overexpressing αB-crystallin is abolished. The synthesis of the endogenous Hsps induced by the heat shock to test for thermotolerance is also blocked by 2-aminopurine. Most likely the protective effect of αB-crystallin requires synthesis of the endogenous heat shock proteins. Translational thermotolerance would then be a co-operative effect of different heat shock proteins. Cells facing stress divert their resources to combating and surviving that stress. For example, during a heat shock, general macromolecular synthesis and processing is inhibited, and the set of transcription units that encode the heat shock proteins (Hsps) 1The abbreviations used are: Hspheat shock proteinsHspsmall heat shock proteinseIF2αeukaryotic initiation factor 2αSGstress granulesRT-PCRreverse transcriptase-PCRDMEMDulbecco's modified Eagle's mediumPKRdouble-stranded RNA-activated kinaseIRESinternal ribosome entry siteFGFfibroblast growth factor. is activated (1.Laszlo A. Exp. Cell Res. 1988; 178: 401-414Crossref PubMed Scopus (71) Google Scholar, 2.Brostrom C.O. Brostrom M.A. Prog. Nucleic Acid Res. Mol. Biol. 1998; 58: 79-125Crossref PubMed Scopus (250) Google Scholar). Synthesis of the Hsps is required for optimal survival of heat (or other) stress. The Hsps are a complex group of proteins, ranging in size between 90 and 20 kDa. The small heat shock proteins (sHsps) belong to a family of proteins distinguished by sharing a common protein domain, the so-called α-crystallin domain (for review, see Ref. 3.de Jong W.W. Leunissen J.A. Voorter C.E. Mol. Biol. Evol. 1993; 10: 103-126PubMed Google Scholar). In man, there are 10 different sHsps (4.Kappé G. Franck E. Verschuure P. Boelens W.C. Leunissen J.A.M. de Jong W.W. Cell Stress Chaperones. 2003; 8: 53-61Crossref PubMed Scopus (383) Google Scholar); of these, Hsp27 and αB-crystallin are traditional heat shock proteins in the sense that their synthesis is induced by a heat shock (5.Kato K. Ito H. Inaguma Y. Prog. Mol. Subcell. Biol. 2002; 28: 129-150Crossref PubMed Scopus (28) Google Scholar). All sHsps, including the stress-inducible sHsps, are constitutively expressed in different tissues; αB-crystallin, for example, is abundant in lens, heart, skeletal muscle, and brain (5.Kato K. Ito H. Inaguma Y. Prog. Mol. Subcell. Biol. 2002; 28: 129-150Crossref PubMed Scopus (28) Google Scholar, 6.Van Montfort R. Slingsby C. Vierling E. Adv. Protein Chem. 2001; 59: 105-156Crossref PubMed Scopus (386) Google Scholar, 7.Davidson S.M. Loones M.T. Duverger O. Morange M. Prog. Mol. Subcell. Biol. 2002; 28: 103-128Crossref PubMed Scopus (22) Google Scholar). The best known property of Hsp27 and of αB-crystallin is their in vitro chaperone activity: they keep their substrates in solution but cannot refold them (for review, see Refs. 6.Van Montfort R. Slingsby C. Vierling E. Adv. Protein Chem. 2001; 59: 105-156Crossref PubMed Scopus (386) Google Scholar and 8.Narberhaus F. Microbiol. Mol. Biol. Rev. 2002; 66: 64-93Crossref PubMed Scopus (470) Google Scholar). In vivo, they might act as a reservoir of unfolded proteins for the large Hsps, which are ATP-dependent refoldases. The sHsps are also thought to stabilize the cytoskeleton during stress (9.Quinlan R. Prog. Mol. Subcell. Biol. 2002; 28: 219-233Crossref PubMed Scopus (77) Google Scholar); in addition, they interact with some components of the apoptotic pathway, thereby protecting the cell from apoptosis (10.Arrigo A.P. Paul C. Ducasse C. Manero F. Kretz-Remy C. Virot S. Javouhey E. Mounier N. Diaz-Latoud C. Prog. Mol. Subcell. Biol. 2002; 28: 185-204Crossref PubMed Scopus (55) Google Scholar). heat shock protein small heat shock proteins eukaryotic initiation factor 2α stress granules reverse transcriptase-PCR Dulbecco's modified Eagle's medium double-stranded RNA-activated kinase internal ribosome entry site fibroblast growth factor. sHsps can be regulated in their activity by phosphorylation. αB-crystallin has three phosphorylation sites. Serine 59 is phosphorylated when cells are stressed, and serines 19 and 45 are found phosphorylated when cells are going into mitosis (11.Hoover H.E. Thuerauf D.J. Martindale J.J. Glembotski C.C. J. Biol. Chem. 2000; 275: 23825-23833Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar, 12.Kato K. Ito H. Kamei K. Inaguma Y. Iwamoto I. Saga S. J. Biol. Chem. 1998; 273: 28346-28354Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar). The overall level of phosphorylation of αB-crystallin remains low (13.Ito H. Okamoto K. Nakayama H. Isobe T. Kato K. J. Biol. Chem. 1997; 272: 29934-29941Abstract Full Text Full Text PDF PubMed Scopus (190) Google Scholar). Hsp27 has two (rodents) or three (man) phosphorylation sites. At normal temperature, Hsp27 is mainly unphosphorylated: after different kinds of stress, including heat shock, Hsp27 is extensively phosphorylated (5.Kato K. Ito H. Inaguma Y. Prog. Mol. Subcell. Biol. 2002; 28: 129-150Crossref PubMed Scopus (28) Google Scholar, 14.Gaestel M. Prog. Mol. Subcell. Biol. 2002; 28: 151-169Crossref PubMed Scopus (40) Google Scholar). For Hsp27 and αB-crystallin, phosphorylation has been to complex in vitro H. A. J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, T. M. A. G. Ducasse C. Paul C. M. A.P. J. M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, H. Kamei K. Iwamoto I. Inaguma Y. Kato K. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google in decrease in chaperone activity T. M. A. G. Ducasse C. Paul C. M. A.P. J. M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, H. Kamei K. Iwamoto I. Inaguma Y. Kato K. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, A. T. N. K. Biol. 2001; PubMed Scopus Google Scholar). Hsp27 cells from heat stress but not from stress T. M. A. G. Ducasse C. Paul C. M. A.P. J. M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, K. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, A.P. Paul C. Ducasse C. O. Kretz-Remy C. Prog. Mol. Subcell. Biol. 2002; 28: PubMed Scopus Google Scholar). Cells a of Hsps of an stress are more to heat stress, a phenomenon known as thermotolerance. can be induced by of a single as Hsp27, or αB-crystallin J. 1997; 66: PubMed Scopus Google Scholar, G. J. J. Biol. Chem. 1993; Full Text PDF PubMed Google Scholar, H. Mol. Biol. PubMed Scopus Google Scholar, S. J. Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus Google Scholar, M. J. Prog. Mol. Subcell. Biol. 2002; 28: PubMed Scopus Google Scholar). In thermotolerant cells, protein synthesis is still rapidly inhibited by heat stress, but protein synthesis recovers faster than in naive heat-shocked cells, a phenomenon known as translational thermotolerance Cell Stress Chaperones. PubMed Scopus Google Scholar, A. J. Biol. Chem. Full Text PDF PubMed Google Scholar, A. J. 1993; PubMed Scopus Google Scholar, A. 1993; Google Scholar). The mechanism of inhibition of translation by a heat shock as by of Ref. PubMed Scopus Google and also the mechanism of translational thermotolerance is still a of The to be the level of translation Phosphorylation and inhibition of is found after stress J. A. J. 2002; PubMed Scopus Google Scholar, 2002; Full Text Full Text PDF PubMed Scopus Google but be as the of in cells not with the level of phosphorylation of J. M. R. J. Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus Google Scholar). The complex also be cap-independent initiation of translation is more than is cap-dependent initiation of translation J. I. P. M. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, Res. 2002; PubMed Scopus Google Scholar). in general translation in cells, but translation of and cap-independent still S. A. J. Biol. Chem. Full Text PDF PubMed Google a that the of translation in cells from heat stress and which that is during a heat shock. translation initiation components of the complex but not the in the as stress granules Hsp27 has been in as M. I. P. J. Cell Biol. PubMed Scopus Google in complex with R. G. 2000; Google Scholar). in is a and are thought to be and there for or into N. S. N. P. J. Cell Biol. 2000; PubMed Scopus Google Scholar). This indicates that during and after stress, are for initiation of translation. translational has been the level of the overall of protein and no has been between cap-dependent and cap-independent translation show that of αB-crystallin or Hsp27 cap-dependent but not cap-independent translation whereas of Hsp70 we show that the phosphorylation state of αB-crystallin or Hsp27 its to translational we show that 2-aminopurine, a kinase inhibitor that as double-stranded RNA-activated kinase N. F. R. Mol. Biol. PubMed Scopus Google Scholar, Y. Y. Y. A. R. 2002; Full Text Full Text PDF PubMed Scopus Google the of translational by of an Cell cells were in Dulbecco's modified Eagle's medium with and and with to of these cells cells with were in Eagle's medium with and and of heat shock were with for cells and for The cells were to a heat shock by in a 45 cells were heat for cells were heat for 45 Cells were during recovery by in of and Protein were by the protein to the for of and of the was on and were blocked for in and and with in in for three in the was with the with a for The were in with and and with in and with after with a cells were in with and to in Cells were for in with and Cells were heat for 45 and for the level of protein synthesis different during At these medium was by of with and and 20 of cells were by in of and for The cell was in of 10 and in a of the were on an the the was in for after with in and and in and the was and results were with after with a cells were with cells were in with and in cells were with a of of of and of a of was and the of was the or and for αB-crystallin, Hsp27, or the as in a after cells were heat for 45 and for activity during recovery cells were in Eagle's medium with and in and after with of of a for the of the was The and αB-crystallin, Hsp27, or were used in a after cells were heat for 45 cells were for 45 Cells were with for the heat shock to the of cells were with and with and Cells were during recovery and for and were in and with different of results of are cells were in of into a of was and the was for on and for of the was with an of At this from three was were for for the was with and then for The was in 45 of and The was with units of of for and was then for 10 The reverse transcription was the synthesis for to the with of and in a of 20 used for the were and as a and The was in a of of a of and and was on of the to test for The was for were for and then was for 90 were after and and on in were after on a system. not with the shock, cells were with and in a with a of of after cells were for 45 The was induced as in the of was to a of 10 after the was in to a and to with a to with was to Cells were after For the cells, was heat shock. Cells were after of recovery with Cells were for and activity and for in heat shock and cells were by or in of and For the was to a with of this was to 20 of the cell temperature, of was For the of was to 20 of the cell were on a for 10 In cells, were for the In cells, were for the of cells in two were in the For the the Hsp70 was from the I. F. Nucleic Res. 8: PubMed Scopus Google and in of the and from the For the the was from S. N. A. M. F. K. A. N. Res. 1988; PubMed Scopus Google and between the Hsp70 and the αB-crystallin was into P. J. G. S. A. PubMed Scopus Google Scholar). The αB-crystallin by P. of and phosphorylation by were into the The Hsp27 and phosphorylation mutants and were a from J. H. A. J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The Hsp70 was by on from heat-shocked The used were and of the Hsp70 were into after the Hsp70 was into the for the and for the The was P. M. de Jong W.W. PubMed Scopus Google Scholar). αB-crystallin but translation in cells was inhibited after a heat shock 45 and not of the endogenous small heat shock proteins Hsp27 and αB-crystallin was after the level of Hsp27 a state after the level of αB-crystallin to to general protein synthesis was inhibited, as heat shock proteins, were still these of a small heat shock protein a of translational thermotolerance these cells were with an for αB-crystallin with to translation after heat shock different were In the was of the Hsp70 the of the in the the of the was between the Hsp70 and the are by the Hsp70 and the after a heat to decrease from to the heat shock, was used as the This is heat and by heat shock. The difference between the by these two is in the The has a and is to be the mechanism for translation cap-dependent translation The the internal ribosome entry site known to be used during stress S. C. S. F. F. H. J. Cell Biol. PubMed Scopus Google and be by of a cap-independent In of this difference in the mechanism of translation we found that the from the was inhibited by whereas that from the was not and not has been to cap-dependent translation initiation but not cap-independent translation initiation N. J. PubMed Scopus Google Scholar). recovery from a heat shock, the from the was than that from the of αB-crystallin significantly the from the but not that from the the not between cells and cells overexpressing αB-crystallin and not the in from the be of an in the of translation. The protective effect of αB-crystallin on the of translation of the the of the heat the level of protection was during recovery from a or heat shock 45 but during recovery from a or more heat shock In with cells, a heat shock 45 was used that cell in their to heat to with cells, the cells to be to 45 for not The level of protection by αB-crystallin the of When more of the αB-crystallin was the of activity from the of the that there is a to the of that can be was not to the of the αB-crystallin that in is not known the level of protection by αB-crystallin these by Hsp70 and Hsp70 and Hsp27 also been to cells with translational thermotolerance J. 1997; 66: PubMed Scopus Google Scholar, A. J. Biol. Chem. Full Text PDF PubMed Google Scholar, R. R. J. 10: PubMed Scopus Google Scholar). we tested of these two heat shock proteins also the of translation of the during recovery from a heat shock. in the results after of Hsp27 are to after of αB-crystallin as Hsp27 not the level of from the or and not but in the presence of Hsp27, the from the that from the the In in the presence of the from both the and the an for a was In the presence of more is for the two sHsps as as the large translational the protection by the sHsps is more and a required for cap-dependent initiation The of and αB-crystallin are phosphorylated during stress. For Hsp27, the of phosphorylation is (5.Kato K. Ito H. Inaguma Y. Prog. Mol. Subcell. Biol. 2002; 28: 129-150Crossref PubMed Scopus (28) Google Scholar, 14.Gaestel M. Prog. Mol. Subcell. Biol. 2002; 28: 151-169Crossref PubMed Scopus (40) Google and phosphorylation is required for thermotolerance K. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, J. P. A. H. J. PubMed Scopus Google Scholar, J. 2002; PubMed Scopus Google Scholar). For αB-crystallin, the of phosphorylation is low Montfort R. Slingsby C. Vierling E. Adv. Protein Chem. 2001; 59: 105-156Crossref PubMed Scopus (386) Google Scholar, H. Okamoto K. Nakayama H. Isobe T. Kato K. J. Biol. Chem. 1997; 272: 29934-29941Abstract Full Text Full Text PDF PubMed Scopus (190) Google and the of phosphorylation in thermotolerance is not test the phosphorylation state of αB-crystallin or Hsp27 their to the translation of the mutants non-phosphorylated and Hsp27 and or phosphorylated and Hsp27 αB-crystallin or Hsp27 were with in phosphorylation of αB-crystallin the protection of of the site which phosphorylation is The mutants of αB-crystallin, however, are more in translation protection In the of Hsp27 was whereas the phosphorylation was as as The in which the phosphorylation site was was as as whereas the in which the phosphorylation site was was than show for activity in translation Hsp27 needs to be whereas αB-crystallin be of of from a the we cannot give a of the of translational thermotolerance by αB-crystallin or Hsp27 as we no of the of would be translation were not inhibited we used a heat shock can we the of translational thermotolerance when αB-crystallin or Hsp27 is overexpressed is to that seen in thermotolerant cells, as the of the and the of or between naive and thermotolerant some of the translational we to cells cells the In these cells, we induced of a of the for to a of we then the the cells with a heat shock of 45 The of in activity during recovery was then in in the presence of αB-crystallin or Hsp27, the of of was significantly than in cells with an not significantly not this effect be by an in translational thermotolerance by the small heat shock proteins. in this the protective effect of αB-crystallin and Hsp27 for 20 In cells, the in cells with in cells after 20 of This difference is likely by in the of the and of their The of translation of the during recovery from a heat shock was also in thermotolerant cells, cells from a heat shock. The of in activity in these cells was not significantly different from that in cells overexpressing αB-crystallin In the presence of αB-crystallin or after a shock, the translational activity was of that found in cells The Translational that both αB-crystallin and Hsp27 are of translational thermotolerance to that found in thermotolerant be that during the heat shock to the synthesis of endogenous heat shock proteins is also is that the translational thermotolerance by of these two small heat shock proteins requires the of heat shock proteins. test this we a of the synthesis of endogenous heat shock proteins. has been N. A. Full Text PDF PubMed Scopus Google that the synthesis of a finding in with the that of the inhibited by 2-aminopurine, is required for the heat shock PubMed Scopus Google Scholar, M. S. A. A. M.A. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). we tested the effect of 2-aminopurine. N. F. R. Mol. Biol. PubMed Scopus Google Scholar, Y. Y. Y. A. R. 2002; Full Text Full Text PDF PubMed Scopus Google and as phosphorylation of is thought to be for inhibition of protein initiation during stress J. A. J. 2002; PubMed Scopus Google Scholar, 2002; Full Text Full Text PDF PubMed Scopus Google with in an in the of the synthesis of endogenous Hsps is not required for the translational the of of in cells, of of Cells from a heat shock are known to a of translation than cells, an effect that has been to inhibition of R. Mol. 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The effect of Hsp70 in be of of the of the Hsp70 used in these is as the level of in cells is of that found in cells after recovery from a heat shock in the of an overexpressed not The in activity in the presence of Hsp70 also be to de synthesis. The Hsp70 has been to be with after a heat shock A. J. Biol. Chem. Full Text PDF PubMed Google and the effect of Hsp70 be on as as on In the of sHsps, cap-dependent synthesis that these proteins The likely of is that sHsps of the in cap-dependent This to be in to the of R. G. 2000; Google that Hsp27 an complex with the by were the heat shock temperature, whereas we the effect of Hsp27 in cells from a heat shock. with the of would a in which Hsp27 (or with and during the heat shock, in of during recovery from a heat shock. a is as would also be in with the of the sHsps as of proteins. For αB-crystallin, there is a between protective activity and chaperone as for this protein phosphorylation its to translational and phosphorylation also its chaperone activity H. Kamei K. Iwamoto I. Inaguma Y. Kato K. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, A. T. N. K. Biol. 2001; PubMed Scopus Google Scholar). we that phosphorylation of Hsp27 not its to translational has been that phosphorylation mutants in vitro chaperone activity T. M. A. G. Ducasse C. Paul C. M. A.P. J. M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). mutants of Hsp27 that cannot be phosphorylated chaperone activity but are in translation for Hsp27, there is no between chaperone activity and translational thermotolerance. αB-crystallin and Hsp27 in the mechanism by which they translational thermotolerance for example, different components of the their mechanism of is the the of translational by sHsps not chaperone The heat shock is by stress. The of the is still but mechanism the of the double-stranded RNA-activated kinase of I. T. J. Biol. Chem. 2000; 275: Full Text Full Text PDF PubMed Scopus Google Scholar, T. M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). In the of double-stranded RNA-activated kinase, Hsp70 is not induced M. S. A. A. M.A. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). Hsp70 is also blocked by N. A. Full Text PDF PubMed Scopus Google Scholar and an effect mediated by inhibition of double-stranded RNA-activated we found that with the protective effect of overexpressing The likely is that the protective effect of αB-crystallin requires the synthesis of endogenous heat shock proteins. Translational thermotolerance would then be a effect of different heat shock proteins. are which heat shock proteins are required in to αB-crystallin or The translational to a heat shock is translation is inhibited, whereas translation is recovery from a heat shock (for see has been that is the factor in both its stress would phosphorylation of and inhibition of translation its inhibition during recovery would to of and to translation has been that the inhibition of during heat shock recovery is to transcription of and inhibition of by R. Mol. Biol. 1998; PubMed Scopus Google Scholar, Nucleic Res. 2002; PubMed Scopus Google Scholar). this mechanism has been to be an of Nucleic Res. 1998; PubMed Scopus Google Scholar). and this into of is required for synthesis of heat shock proteins and for the recovery of the inhibition of during heat shock and during recovery from the heat shock than protein synthesis. The mechanism of the of protein synthesis in cells remains of is in cells, is not a in cells might in a of of than phosphorylation by I. Y. H. R. J. 2003; PubMed Scopus Google Scholar). Hsp27 and αB-crystallin are constitutively expressed in a of finding that these proteins these with translational in with heat shock proteins, is of that the translational thermotolerance by the sHsps is for cap-dependent The sHsps can the translation by translation of cap-dependent during stress. is more and more that in the activity of general initiation a effect on the translational of 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). would be of to there is also a between sHsps and the translation initiation in the of stress. The level of sHsps then be of the of the translational of a P. of for the αB-crystallin J. for the for of the αB-crystallin and I. for of the Hsp70