Heat Shock Factor 1 Represses Ras-induced Transcriptional Activation of the c-fos Gene

Heat shock factor 1, the critical molecular regulator of the stress response is conserved throughout eukaryotic organisms and activates the transcription of heat shock genes. We now show that heat shock factor 1 inhibits the expression of c-fos, an immediate early gene that controls responses to extracellular stimuli for growth and differentiation. Heat shock factor 1 inhibits the transcription of the c-fos gene and antagonizes the activating effects of the signal transducing protein Ras on the c-fos promoter and on the promoter of another Ras responsive gene uPA. This property was specific for heat shock factor 1; c-fos repression was not seen with the structurally related protein heat shock factor 2. Repression involved different molecular mechanisms compared with those involved in transcriptional activation by heat shock factor 1 and specifically did not require binding to the c-fos promoter. Thus, in addition to its known role as a transcriptional activator of the cellular heat shock response, heat shock factor 1 also antagonizes the expression of Fos, a key component of the ubiquitous AP-1 transcription factor complex and as such could influence multiple aspects of cell regulation. Heat shock factor 1, the critical molecular regulator of the stress response is conserved throughout eukaryotic organisms and activates the transcription of heat shock genes. We now show that heat shock factor 1 inhibits the expression of c-fos, an immediate early gene that controls responses to extracellular stimuli for growth and differentiation. Heat shock factor 1 inhibits the transcription of the c-fos gene and antagonizes the activating effects of the signal transducing protein Ras on the c-fos promoter and on the promoter of another Ras responsive gene uPA. This property was specific for heat shock factor 1; c-fos repression was not seen with the structurally related protein heat shock factor 2. Repression involved different molecular mechanisms compared with those involved in transcriptional activation by heat shock factor 1 and specifically did not require binding to the c-fos promoter. Thus, in addition to its known role as a transcriptional activator of the cellular heat shock response, heat shock factor 1 also antagonizes the expression of Fos, a key component of the ubiquitous AP-1 transcription factor complex and as such could influence multiple aspects of cell regulation. Heat shock results in the activation of a pre-existing transcription factor, heat shock factor 1 (HSF1) 1The abbreviations used are: HSF1, heat shock factor 1; HSF2, heat shock factor 2; hsp, heat shock protein; uPa, urokinase-type plasminogen activator; CHO, Chinese hamster ovary; MAPK, mitogen-activated protein kinase; TCF, ternary complex factor; SRE, serum response element; EMSA, electrophoretic mobility shift assay; FCS, fetal calf serum; SRF, serum response factor. 1The abbreviations used are: HSF1, heat shock factor 1; HSF2, heat shock factor 2; hsp, heat shock protein; uPa, urokinase-type plasminogen activator; CHO, Chinese hamster ovary; MAPK, mitogen-activated protein kinase; TCF, ternary complex factor; SRE, serum response element; EMSA, electrophoretic mobility shift assay; FCS, fetal calf serum; SRF, serum response factor. through a process that includes trimerization and nuclear translocation (1Voellmy R. Crit. Rev. Eukaryotic Gene Expression. 1994; 4: 357-401PubMed Google Scholar, 2Wu C. Annu. Rev. Cell. Dev. Biol. 1995; 11: 441-469Crossref PubMed Scopus (963) Google Scholar, 3Peristic O. Xiao H. Lis J.T. Cell. 1989; 59: 797-806Abstract Full Text PDF PubMed Scopus (322) Google Scholar). Activated HSF1 binds to heat shock elements (HSE) in heat shock protein (hsp) gene promoters and induces expression of hsps involved in the assembly, folding, and transport of other proteins and conferring thermotolerence on expressing cells (4Price B.D. Calderwood S.K. Mol. Cell. Biol. 1991; 11: 3365-3368Crossref PubMed Scopus (121) Google Scholar, 5Haas I.G. Wabl M. Nature. 1983; 306: 387-389Crossref PubMed Scopus (585) Google Scholar, 6Oppermann J. Horwich H.C. Neupert W. Ulrich-Hartl F. Nature. 1989; 341: 125-130Crossref PubMed Scopus (472) Google Scholar, 7Georgopolis C. Welsh W.J. Annu. Rev. Cell Biol. 1993; 22: 631-634Google Scholar). Our recent studies indicate that in addition to being a transcriptional activator, HSF1 functions as a repressor of a number of genes including IL1B (8Cahill C.M. Waterman W.R. Xie Y. Auron P.E. Calderwood S.K. J. Biol. Chem. 1996; 271: 24874-27879Abstract Full Text Full Text PDF PubMed Google Scholar). This suggests that at elevated temperatures HSF1 possesses both activation and suppression functions, depending on the nature of the target promoter (1Voellmy R. Crit. Rev. Eukaryotic Gene Expression. 1994; 4: 357-401PubMed Google Scholar, 2Wu C. Annu. Rev. Cell. Dev. Biol. 1995; 11: 441-469Crossref PubMed Scopus (963) Google Scholar, 8Cahill C.M. Waterman W.R. Xie Y. Auron P.E. Calderwood S.K. J. Biol. Chem. 1996; 271: 24874-27879Abstract Full Text Full Text PDF PubMed Google Scholar). The function of the heat shock response in mammals is somewhat mysterious considering the tight regulation of body temperature in homeotherms. However, the response may have become adapted to function during fever, the neuroendocrine response to disease that modulates elevation in body temperature (9Kruger M.J. Kozac W. Conn C.A. Leon L.R. Sosynski D. Infect. Dis. North Am. 1996; 10: 1-20Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar). Because one function of interleukin 1ॆ, the product of the IL1B gene and a target for HSF1 repression is the mediation of fever, HSF1 could function as a feedback inhibitor of ILIB during fever (8Cahill C.M. Waterman W.R. Xie Y. Auron P.E. Calderwood S.K. J. Biol. Chem. 1996; 271: 24874-27879Abstract Full Text Full Text PDF PubMed Google Scholar). We are interested to know whether HSF1 affects other genes involved in cell proliferation, differentiation, and viral infection that might be involved in the heat shock response and the mediation of fever. One such gene is c-fos, an early response gene involved in regulating normal cellular proliferation and differentiation as well as being expressed in many types of tumors (10Holt J.T. Gopal V. Moulton A.D. Nienhuis A.W. Proc. Natl. Acad. Sci. U. S. PubMed Scopus Google Scholar, M.J. PubMed Scopus Google Scholar). the nuclear with proteins to a transcription factor with AP-1 that is a nuclear target of the Ras and is a in the of H. 1989; Full Text PDF PubMed Scopus Google Scholar, M. Nature. 1994; PubMed Scopus Google Scholar, R. J. 1995; PubMed Scopus Google Scholar). as a signal in a to other signal the to nuclear such as the transcription Y. H. M. Annu. Rev. 1991; PubMed Scopus Google Scholar). We have the of HSF1 on the expression of the c-fos gene and the of the c-fos promoter in and Chinese hamster promoter was and the promoter was a and of of expression and urokinase-type plasminogen activator gene M. C. the cell was the and and was by the gene promoter to of at the was by the gene promoter S. 1996; PubMed Scopus Google to at the and was by the c-fos promoter to to the transcription 2. a of the c-fos promoter was to was by to promoter Y. H. M. Annu. Rev. 1991; PubMed Scopus Google HSF1 S.K. J. C. Proc. Natl. Acad. Sci. U. S. 1991; PubMed Scopus Google was the expression at the as indicate the of the in and S. in was the and to the to of early promoter and and was the and to the and and was by HSF1 with the with and was HSF1 at to the binding was by HSF1 at the and with the was by with a as C. PubMed Scopus Google was on and to as (8Cahill C.M. Waterman W.R. Xie Y. Auron P.E. Calderwood S.K. J. Biol. Chem. 1996; 271: 24874-27879Abstract Full Text Full Text PDF PubMed Google Scholar). by with a c-fos and a C. Calderwood S.K. Gene PubMed Scopus Google with a and cells at and for to with expression and expression as C.M. Xie Y. M.J. 1995; PubMed Scopus Google Scholar). Cell as and and to the and was as C.M. Xie Y. M.J. 1995; PubMed Scopus Google Scholar). was to was used as an are expressed as of of with multiple was for of cells in for was to cells and to W. 1989; PubMed Scopus Google with a and by as (8Cahill C.M. Waterman W.R. Xie Y. Auron P.E. Calderwood S.K. J. Biol. Chem. 1996; 271: 24874-27879Abstract Full Text Full Text PDF PubMed Google studies indicate that the of c-fos is by heat shock at through transcriptional repression of the c-fos promoter c-fos repression did not require the binding of HSF1 to the c-fos promoter a HSF1 in binding and transcriptional activating function the c-fos promoter and was for HSF1 binding to the promoter The mechanisms of c-fos repression by HSF1 with those transcriptional are on HSF1 binding to promoters (1Voellmy R. Crit. Rev. Eukaryotic Gene Expression. 1994; 4: 357-401PubMed Google Scholar, 2Wu C. Annu. Rev. Cell. Dev. Biol. 1995; 11: 441-469Crossref PubMed Scopus (963) Google Scholar). repression a number of mechanisms S. C. Dev. PubMed Scopus Google Scholar, A.D. Annu. Rev. Cell. Biol. 1993; PubMed Scopus Google Scholar, S. M. Dev. 1996; 10: PubMed Scopus Google Scholar). The the of activating binding to elements is for HSF1 repression the that HSF1 activates promoters c-fos suggests that HSF1 not the of transcription HSF1 may the c-fos promoter by with an signal component a specific regulation of the is serum activation of the Ras and of serum response factor to to the and complex with transcription R. J. 1995; PubMed Scopus Google Scholar, C.M. Xie Y. M.J. 1995; PubMed Scopus Google Scholar, D. M. Dev. 1995; Scopus Google Scholar, H. A.D. P.E. Nature. PubMed Scopus Google Scholar). AP-1 may also be by Ras and to of the c-fos promoter as as the H. 1989; Full Text PDF PubMed Scopus Google Scholar, M. Nature. 1994; PubMed Scopus Google Scholar). Because HSF1 is to the at elevated of Ras c-fos gene transcription by HSF1 to the the are in translocation to the of and c-fos activation R. J. 1995; PubMed Scopus Google Scholar, H. A.D. P.E. Nature. PubMed Scopus Google Scholar, C.M. R. Cell. 1993; Full Text PDF PubMed Scopus Google Scholar). The effects of HSF1 are to at a activation indicate that heat shock is a activator of an and the protein that are involved in AP-1 activation are by heat J. 1996; PubMed Scopus Google Scholar). and S. HSF1 could with with the complex of and to on the c-fos promoter R. J. 1995; PubMed Scopus Google Scholar, C.M. Xie Y. M.J. 1995; PubMed Scopus Google Scholar, D. M. Dev. 1995; Scopus Google Scholar, R. 1991; Google Scholar). addition the is also by HSF1 binding for and AP-1 that could be by HSF1 C.A. C. Mol. Cell. Biol. 1996; PubMed Scopus Google Scholar). for HSF1 function of the c-fos promoter is that the of a to the c-fos many of the for is also by HSF1 HSF1 could with a factor to specifically genes such as c-fos and and the effects of activation by signal repression is specific for HSF1 and was not with a that may involved in repression The HSF1 and are in the binding and trimerization in in the and activation (1Voellmy R. Crit. Rev. Eukaryotic Gene Expression. 1994; 4: 357-401PubMed Google Scholar, 2Wu C. Annu. Rev. Cell. Dev. Biol. 1995; 11: 441-469Crossref PubMed Scopus (963) Google Scholar, S.K. J. C. Proc. Natl. Acad. Sci. U. S. 1991; PubMed Scopus Google Scholar, Proc. Natl. Acad. U. S. 1991; PubMed Scopus Google V. C. Dev. 1991; PubMed Scopus Google Scholar). repression might be the HSF1 functions as a Ras by activation of the c-fos promoter. repression may a component of HSF1 function in the cellular heat shock response as well as in such as fever elevated Heat shock results in the activation of a pre-existing transcription factor, heat shock factor 1 (HSF1) 1The abbreviations used are: HSF1, heat shock factor 1; HSF2, heat shock factor 2; hsp, heat shock protein; uPa, urokinase-type plasminogen activator; CHO, Chinese hamster ovary; MAPK, mitogen-activated protein kinase; TCF, ternary complex factor; SRE, serum response element; EMSA, electrophoretic mobility shift assay; FCS, fetal calf serum; SRF, serum response factor. 1The abbreviations used are: HSF1, heat shock factor 1; HSF2, heat shock factor 2; hsp, heat shock protein; uPa, urokinase-type plasminogen activator; CHO, Chinese hamster ovary; MAPK, mitogen-activated protein kinase; TCF, ternary complex factor; SRE, serum response element; EMSA, electrophoretic mobility shift assay; FCS, fetal calf serum; SRF, serum response factor. through a process that includes trimerization and nuclear translocation (1Voellmy R. Crit. Rev. Eukaryotic Gene Expression. 1994; 4: 357-401PubMed Google Scholar, 2Wu C. Annu. Rev. Cell. Dev. Biol. 1995; 11: 441-469Crossref PubMed Scopus (963) Google Scholar, 3Peristic O. Xiao H. Lis J.T. Cell. 1989; 59: 797-806Abstract Full Text PDF PubMed Scopus (322) Google Scholar). Activated HSF1 binds to heat shock elements (HSE) in heat shock protein (hsp) gene promoters and induces expression of hsps involved in the assembly, folding, and transport of other proteins and conferring thermotolerence on expressing cells (4Price B.D. Calderwood S.K. Mol. Cell. Biol. 1991; 11: 3365-3368Crossref PubMed Scopus (121) Google Scholar, 5Haas I.G. Wabl M. Nature. 1983; 306: 387-389Crossref PubMed Scopus (585) Google Scholar, 6Oppermann J. Horwich H.C. Neupert W. Ulrich-Hartl F. Nature. 1989; 341: 125-130Crossref PubMed Scopus (472) Google Scholar, 7Georgopolis C. Welsh W.J. Annu. Rev. Cell Biol. 1993; 22: 631-634Google Scholar). Our recent studies indicate that in addition to being a transcriptional activator, HSF1 functions as a repressor of a number of genes including IL1B (8Cahill C.M. Waterman W.R. Xie Y. Auron P.E. Calderwood S.K. J. Biol. Chem. 1996; 271: 24874-27879Abstract Full Text Full Text PDF PubMed Google Scholar). This suggests that at elevated temperatures HSF1 possesses both activation and suppression functions, depending on the nature of the target promoter (1Voellmy R. Crit. Rev. Eukaryotic Gene Expression. 1994; 4: 357-401PubMed Google Scholar, 2Wu C. Annu. Rev. Cell. Dev. Biol. 1995; 11: 441-469Crossref PubMed Scopus (963) Google Scholar, 8Cahill C.M. Waterman W.R. Xie Y. Auron P.E. Calderwood S.K. J. Biol. Chem. 1996; 271: 24874-27879Abstract Full Text Full Text PDF PubMed Google Scholar). The function of the heat shock response in mammals is somewhat mysterious considering the tight regulation of body temperature in homeotherms. However, the response may have become adapted to function during fever, the neuroendocrine response to disease that modulates elevation in body temperature (9Kruger M.J. Kozac W. Conn C.A. Leon L.R. Sosynski D. Infect. Dis. North Am. 1996; 10: 1-20Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar). Because one function of interleukin 1ॆ, the product of the IL1B gene and a target for HSF1 repression is the mediation of fever, HSF1 could function as a feedback inhibitor of ILIB during fever (8Cahill C.M. Waterman W.R. Xie Y. Auron P.E. Calderwood S.K. J. Biol. Chem. 1996; 271: 24874-27879Abstract Full Text Full Text PDF PubMed Google Scholar). We are interested to know whether HSF1 affects other genes involved in cell proliferation, differentiation, and viral infection that might be involved in the heat shock response and the mediation of fever. One such gene is c-fos, an early response gene involved in regulating normal cellular proliferation and differentiation as well as being expressed in many types of tumors (10Holt J.T. Gopal V. Moulton A.D. Nienhuis A.W. Proc. Natl. Acad. Sci. U. S. PubMed Scopus Google Scholar, M.J. PubMed Scopus Google Scholar). the nuclear with proteins to a transcription factor with AP-1 that is a nuclear target of the Ras and is a in the of H. 1989; Full Text PDF PubMed Scopus Google Scholar, M. Nature. 1994; PubMed Scopus Google Scholar, R. J. 1995; PubMed Scopus Google Scholar). as a signal in a to other signal the to nuclear such as the transcription Y. H. M. Annu. Rev. 1991; PubMed Scopus Google Scholar). We have the of HSF1 on the expression of the c-fos gene and the of the c-fos promoter in and Chinese hamster promoter was and the promoter was a and of of expression and urokinase-type plasminogen activator gene M. C. the cell was the and and was by the gene promoter to of at the was by the gene promoter S. 1996; PubMed Scopus Google to at the and was by the c-fos promoter to to the transcription 2. a of the c-fos promoter was to was by to promoter Y. H. M. Annu. Rev. 1991; PubMed Scopus Google HSF1 S.K. J. C. Proc. Natl. Acad. Sci. U. S. 1991; PubMed Scopus Google was the expression at the as indicate the of the in and S. in was the and to the to of early promoter and and was the and to the and and was by HSF1 with the with and was HSF1 at to the binding was by HSF1 at the and with the was by with a as C. PubMed Scopus Google was on and to as (8Cahill C.M. Waterman W.R. Xie Y. Auron P.E. Calderwood S.K. J. Biol. Chem. 1996; 271: 24874-27879Abstract Full Text Full Text PDF PubMed Google Scholar). by with a c-fos and a C. Calderwood S.K. Gene PubMed Scopus Google with a and cells at and for to with expression and expression as C.M. Xie Y. M.J. 1995; PubMed Scopus Google Scholar). Cell as and and to the and was as C.M. Xie Y. M.J. 1995; PubMed Scopus Google Scholar). was to was used as an are expressed as of of with multiple was for of cells in for was to cells and to W. 1989; PubMed Scopus Google with a and by as (8Cahill C.M. Waterman W.R. Xie Y. Auron P.E. Calderwood S.K. J. Biol. Chem. 1996; 271: 24874-27879Abstract Full Text Full Text PDF PubMed Google Scholar). promoter was and the promoter was a and of of expression and urokinase-type plasminogen activator gene M. C. the cell was the and and was by the gene promoter to of at the was by the gene promoter S. 1996; PubMed Scopus Google to at the and was by the c-fos promoter to to the transcription 2. a of the c-fos promoter was to was by to promoter Y. H. M. Annu. Rev. 1991; PubMed Scopus Google HSF1 S.K. J. C. Proc. Natl. Acad. Sci. U. S. 1991; PubMed Scopus Google was the expression at the as indicate the of the in and S. in was the and to the to of early promoter and and was the and to the and and was by HSF1 with the with and was HSF1 at to the binding was by HSF1 at the and with the was by with a as C. PubMed Scopus Google Scholar). was by the gene promoter to of at the was by the gene promoter S. 1996; PubMed Scopus Google to at the and was by the c-fos promoter to to the transcription 2. a of the c-fos promoter was to was by to promoter Y. H. M. Annu. Rev. 1991; PubMed Scopus Google HSF1 S.K. J. C. Proc. Natl. Acad. Sci. U. S. 1991; PubMed Scopus Google was the expression at the as indicate the of the in and S. in was the and to the to of early promoter and and was the and to the and and was by HSF1 with the with and was HSF1 at to the binding was by HSF1 at the and with the was by with a as C. PubMed Scopus Google Scholar). was by the gene promoter to of at the was by the gene promoter S. 1996; PubMed Scopus Google to at the and was by the c-fos promoter to to the transcription 2. a of the c-fos promoter was to was by to promoter Y. H. M. Annu. Rev. 1991; PubMed Scopus Google Scholar). was by the gene promoter to of at the was by the gene promoter S. 1996; PubMed Scopus Google to at the and was by the c-fos promoter to to the transcription 2. a of the c-fos promoter was to was by to promoter Y. H. M. Annu. Rev. 1991; PubMed Scopus Google Scholar). HSF1 S.K. J. C. Proc. Natl. Acad. Sci. U. S. 1991; PubMed Scopus Google was the expression at the as indicate the of the in and S. in was the and to the to of early promoter and and was the and to the and and was by HSF1 with the with and was HSF1 at to the binding was by HSF1 at the and with the was by with a as C. PubMed Scopus Google Scholar). HSF1 S.K. J. C. Proc. Natl. Acad. Sci. U. S. 1991; PubMed Scopus Google was the expression at the as indicate the of the in and S. in was the and to the to of early promoter and and was the and to the and and was by HSF1 with the with and was HSF1 at to the binding was by HSF1 at the and with the was by with a as C. PubMed Scopus Google Scholar). was on and to as (8Cahill C.M. Waterman W.R. Xie Y. Auron P.E. Calderwood S.K. J. Biol. Chem. 1996; 271: 24874-27879Abstract Full Text Full Text PDF PubMed Google Scholar). by with a c-fos and a C. Calderwood S.K. Gene PubMed Scopus Google with a was on and to as (8Cahill C.M. Waterman W.R. Xie Y. Auron P.E. Calderwood S.K. J. Biol. Chem. 1996; 271: 24874-27879Abstract Full Text Full Text PDF PubMed Google Scholar). by with a c-fos and a C. Calderwood S.K. Gene PubMed Scopus Google with a and cells at and for to with expression and expression as C.M. Xie Y. M.J. 1995; PubMed Scopus Google Scholar). Cell as and and to the and was as C.M. Xie Y. M.J. 1995; PubMed Scopus Google Scholar). was to was used as an are expressed as of of with multiple was for of cells at and for to with expression and expression as C.M. Xie Y. M.J. 1995; PubMed Scopus Google Scholar). Cell as and and to the and was as C.M. Xie Y. M.J. 1995; PubMed Scopus Google Scholar). was to was used as an are expressed as of of with multiple was for of cells in for was to cells and cells in for was to cells and to W. 1989; PubMed Scopus Google with a and by as (8Cahill C.M. Waterman W.R. Xie Y. Auron P.E. Calderwood S.K. J. Biol. Chem. 1996; 271: 24874-27879Abstract Full Text Full Text PDF PubMed Google Scholar). to W. 1989; PubMed Scopus Google with a and by as (8Cahill C.M. Waterman W.R. Xie Y. Auron P.E. Calderwood S.K. J. Biol. Chem. 1996; 271: 24874-27879Abstract Full Text Full Text PDF PubMed Google Scholar). studies indicate that the of c-fos is by heat shock at through transcriptional repression of the c-fos promoter c-fos repression did not require the binding of HSF1 to the c-fos promoter a HSF1 in binding and transcriptional activating function the c-fos promoter and was for HSF1 binding to the promoter The mechanisms of c-fos repression by HSF1 with those transcriptional are on HSF1 binding to promoters (1Voellmy R. Crit. Rev. Eukaryotic Gene Expression. 1994; 4: 357-401PubMed Google Scholar, 2Wu C. Annu. Rev. Cell. Dev. Biol. 1995; 11: 441-469Crossref PubMed Scopus (963) Google Scholar). repression a number of mechanisms S. C. Dev. PubMed Scopus Google Scholar, A.D. Annu. Rev. Cell. Biol. 1993; PubMed Scopus Google Scholar, S. M. Dev. 1996; 10: PubMed Scopus Google Scholar). The the of activating binding to elements is for HSF1 repression the that HSF1 activates promoters c-fos suggests that HSF1 not the of transcription HSF1 may the c-fos promoter by with an signal component a specific regulation of the is serum activation of the Ras and of serum response factor to to the and complex with transcription R. J. 1995; PubMed Scopus Google Scholar, C.M. Xie Y. M.J. 1995; PubMed Scopus Google Scholar, D. M. Dev. 1995; Scopus Google Scholar, H. A.D. P.E. Nature. PubMed Scopus Google Scholar). AP-1 may also be by Ras and to of the c-fos promoter as as the H. 1989; Full Text PDF PubMed Scopus Google Scholar, M. Nature. 1994; PubMed Scopus Google Scholar). Because HSF1 is to the at elevated of Ras c-fos gene transcription by HSF1 to the the are in translocation to the of and c-fos activation R. J. 1995; PubMed Scopus Google Scholar, H. A.D. P.E. Nature. PubMed Scopus Google Scholar, C.M. R. Cell. 1993; Full Text PDF PubMed Scopus Google Scholar). The effects of HSF1 are to at a activation indicate that heat shock is a activator of an and the protein that are involved in AP-1 activation are by heat J. 1996; PubMed Scopus Google Scholar). and S. HSF1 could with with the complex of and to on the c-fos promoter R. J. 1995; PubMed Scopus Google Scholar, C.M. Xie Y. M.J. 1995; PubMed Scopus Google Scholar, D. M. Dev. 1995; Scopus Google Scholar, R. 1991; Google Scholar). addition the is also by HSF1 binding for and AP-1 that could be by HSF1 C.A. C. Mol. Cell. Biol. 1996; PubMed Scopus Google Scholar). for HSF1 function of the c-fos promoter is that the of a to the c-fos many of the for is also by HSF1 HSF1 could with a factor to specifically genes such as c-fos and and the effects of activation by signal repression is specific for HSF1 and was not with a that may involved in repression The HSF1 and are in the binding and trimerization in in the and activation (1Voellmy R. Crit. Rev. Eukaryotic Gene Expression. 1994; 4: 357-401PubMed Google Scholar, 2Wu C. Annu. Rev. Cell. Dev. Biol. 1995; 11: 441-469Crossref PubMed Scopus (963) Google Scholar, S.K. J. C. Proc. Natl. Acad. Sci. U. S. 1991; PubMed Scopus Google Scholar, Proc. Natl. Acad. U. S. 1991; PubMed Scopus Google V. C. Dev. 1991; PubMed Scopus Google Scholar). repression might be the HSF1 functions as a Ras by activation of the c-fos promoter. repression may a component of HSF1 function in the cellular heat shock response as well as in such as fever elevated studies indicate that the of c-fos is by heat shock at through transcriptional repression of the c-fos promoter c-fos repression did not require the binding of HSF1 to the c-fos promoter a HSF1 in binding and transcriptional activating function the c-fos promoter and was for HSF1 binding to the promoter The mechanisms of c-fos repression by HSF1 with those transcriptional are on HSF1 binding to promoters (1Voellmy R. Crit. Rev. Eukaryotic Gene Expression. 1994; 4: 357-401PubMed Google Scholar, 2Wu C. Annu. Rev. Cell. Dev. Biol. 1995; 11: 441-469Crossref PubMed Scopus (963) Google Scholar). repression a number of mechanisms S. C. Dev. PubMed Scopus Google Scholar, A.D. Annu. Rev. Cell. Biol. 1993; PubMed Scopus Google Scholar, S. M. Dev. 1996; 10: PubMed Scopus Google Scholar). The the of activating binding to elements is for HSF1 repression the that HSF1 activates promoters c-fos suggests that HSF1 not the of transcription HSF1 may the c-fos promoter by with an signal component a specific regulation of the is serum activation of the Ras and of serum response factor to to the and complex with transcription R. J. 1995; PubMed Scopus Google Scholar, C.M. Xie Y. M.J. 1995; PubMed Scopus Google Scholar, D. M. Dev. 1995; Scopus Google Scholar, H. A.D. P.E. Nature. PubMed Scopus Google Scholar). AP-1 may also be by Ras and to of the c-fos promoter as as the H. 1989; Full Text PDF PubMed Scopus Google Scholar, M. Nature. 1994; PubMed Scopus Google Scholar). Because HSF1 is to the at elevated of Ras c-fos gene transcription by HSF1 to the the are in translocation to the of and c-fos activation R. J. 1995; PubMed Scopus Google Scholar, H. A.D. P.E. Nature. PubMed Scopus Google Scholar, C.M. R. Cell. 1993; Full Text PDF PubMed Scopus Google Scholar). The effects of HSF1 are to at a activation indicate that heat shock is a activator of an and the protein that are involved in AP-1 activation are by heat J. 1996; PubMed Scopus Google Scholar). and S. HSF1 could with with the complex of and to on the c-fos promoter R. J. 1995; PubMed Scopus Google Scholar, C.M. Xie Y. M.J. 1995; PubMed Scopus Google Scholar, D. M. Dev. 1995; Scopus Google Scholar, R. 1991; Google Scholar). addition the is also by HSF1 binding for and AP-1 that could be by HSF1 C.A. C. Mol. Cell. Biol. 1996; PubMed Scopus Google Scholar). for HSF1 function of the c-fos promoter is that the of a to the c-fos many of the for is also by HSF1 HSF1 could with a factor to specifically genes such as c-fos and and the effects of activation by signal c-fos repression is specific for HSF1 and was not with a that may involved in repression The HSF1 and are in the binding and trimerization in in the and activation (1Voellmy R. Crit. Rev. Eukaryotic Gene Expression. 1994; 4: 357-401PubMed Google Scholar, 2Wu C. Annu. Rev. Cell. Dev. Biol. 1995; 11: 441-469Crossref PubMed Scopus (963) Google Scholar, S.K. J. C. Proc. Natl. Acad. Sci. U. S. 1991; PubMed Scopus Google Scholar, Proc. Natl. Acad. U. S. 1991; PubMed Scopus Google V. C. Dev. 1991; PubMed Scopus Google Scholar). repression might be the HSF1 functions as a Ras by activation of the c-fos promoter. repression may a component of HSF1 function in the cellular heat shock response as well as in such as fever elevated