HSF4, a New Member of the Human Heat Shock Factor Family Which Lacks Properties of a Transcriptional Activator

Nakai, Asami; Tanabe, Masako; Kawazoe, Yoshinori; Inazawa, Johji; Morimoto, Richard I.; Nagata, Kazuhiro

doi:10.1128/mcb.17.1.469

Cited by 311 publications

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References 41 publications

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“…Its expression is regulated in a tissue-specific manner [5,16]. The Hsf4 gene generates both an activator or a repressor of heat shock genes by alternative splicing; the tissue-specificity of the two forms may create a modulation of expression of hsps in the different tissues.…”

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confidence: 99%

“…We show that embryonic HSF2 prefers sites containing three or four nGAAm inverted pentamers and that its optimal binding sequence contains the 8-mer palindromic core 5¢-TTCTAGAA-3¢. The consensus binding sequence for the embryonic HSF2 will be very helpful to identify new targets for this factor, during developmental and differentiation processes.Keywords: heat shock transcription factor-2; protein purification; cooperativity; SELEX; consensus binding sequence.Heat shock factor 2 (HSF2) belongs to the vertebrate heat shock factor family that also includes HSF1, HSF3 and HSF4 [1][2][3][4][5]. The members of the HSF family are defined by their ability to specifically bind the regulatory sequence heat shock element (HSE) [6].…”

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confidence: 99%

“…Heat shock factor 2 (HSF2) belongs to the vertebrate heat shock factor family that also includes HSF1, HSF3 and HSF4 [1][2][3][4][5]. The members of the HSF family are defined by their ability to specifically bind the regulatory sequence heat shock element (HSE) [6].…”

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confidence: 99%

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Determination of the consensus binding sequence for the purified embryonic heat shock factor 2

Manuel¹,

Rallu²,

Loones³

et al. 2002

European Journal of Biochemistry

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Heat shock transcription factors (HSFs) are characterized by their ability, upon activation, to bind to heat shock response elements (HSE) present in the promoter of their target genes. HSE are composed of inverted repeats of the pentamer nGAAm. In this study, we compare the embryonic HSF2 protein, purified from F9 embryonal carcinoma cells tumor, and the in vitro synthesized HSF2. We show that the context of HSF2 synthesis influences its thermosensitivity and DNA-binding properties. Therefore, we determined the consensus binding sequence for the purified embryonic HSF2 by the technique of systematic evolution of ligands by exponential enrichment (SELEX). We show that embryonic HSF2 prefers sites containing three or four nGAAm inverted pentamers and that its optimal binding sequence contains the 8-mer palindromic core 5¢-TTCTAGAA-3¢. The consensus binding sequence for the embryonic HSF2 will be very helpful to identify new targets for this factor, during developmental and differentiation processes.Keywords: heat shock transcription factor-2; protein purification; cooperativity; SELEX; consensus binding sequence.Heat shock factor 2 (HSF2) belongs to the vertebrate heat shock factor family that also includes HSF1, HSF3 and HSF4 [1][2][3][4][5]. The members of the HSF family are defined by their ability to specifically bind the regulatory sequence heat shock element (HSE) [6]. Located in the regulatory regions of heat shock genes, HSE consists of the inverted repeat of a basal element nGAAm [7]. Two inverted repeats are sufficient for Drosophila HSF binding, but optimal binding is obtained with three repeats [8]. In agreement with this observation, the activated form of HSFs has been demonstrated to be a trimer in yeast [9], in Drosophila [10], in human [11,12] or in mouse [13]. The HSE-binding activity of heat shock factors is not constitutive, but induced by various stresses, by differentiation or developmental processes. HSF1 and HSF3 are activated by stresses that elicit the so-called Ôheat shock responseÕ and induce the transcription of heat shock genes. HSF1 corresponds to the paradigm member of the family and is the functional homolog, for its function in the heat shock response, of the unique HSF found in yeast and Drosophila. Avian HSF3 is activated by more severe stresses than HSF1, but is also required for an optimal response to stress [14,15]. Indeed, avian cells expressing HSF1, but in which the HSF3 gene has been disrupted, exhibit a diminished response to stress, even at mild heat shock temperatures [14]. Athough heterotrimers were never detected, HSFs may interact with each other in a more complex way.HSF4 is an exception and constitutively binds DNA as a trimer in the absence of stress. Its expression is regulated in a tissue-specific manner [5,16]. The Hsf4 gene generates both an activator or a repressor of heat shock genes by alternative splicing; the tissue-specificity of the two forms may create a modulation of expression of hsps in the different tissues.In contrast to HSF1 and HSF3, HSF2 is no...

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Determination of the consensus binding sequence for the purified embryonic heat shock factor 2

Manuel¹,

Rallu²,

Loones³

et al. 2002

European Journal of Biochemistry

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“…HSP synthesis is transcriptionally regulated by a family of transcription factors called heat shock factors (HSFs). Four HSFs have been identified: HSF1, HSF2, HSF3, and HSF4 (25,26,33,36); of these, HSF1 is the most important in the heart. After stress, HSF trimerizes and translocates to the nucleus, where it binds to heat shock element (HSE, a promotor region upstream from the HSP genes) to initiate transcription (23).…”

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HSP70.1 and -70.3 are required for late-phase protection induced by ischemic preconditioning of mouse hearts

Hampton

Shimamoto

Rothnie

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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“…The chicken erythroblastic cell line HD6 [3] is activated by heat-shock and by exposure to other environmen-was maintained in HD6 medium [434 ml Dulbecco's modified tal or physiological stresses [1,27]. In avian cells, HSF3 is an-eagle medium (DMEM), 40 ml fetal calf serum, 10 ml chicken other heat-shock-responsive factor which is co-expressed with serum, 5 ml 100ϫnonessential amino acids, 10 ml 0.5 µg/ml hy-HSF1 [21,22]. Generation of a HSF3-deficient chicken B lym-poxanthine in 0.5 M Hepes, pH 7.3, 2.5 ml dimethyl sulfoxide phocyte line revealed that HSF3 is necessary for the burst activa-and 0.5 ml 0.1 mg/ml biotin].…”

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Proteasome inhibition leads to the activation of all members of the heat‐shock‐factor family

Kawazoe

Nakai

Tanabe

et al. 1998

European Journal of Biochemistry

127

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Heat-shock proteins and molecular chaperones are involved in various cellular metabolic processes including protein synthesis and degradation. These expressions are elevated at the level of transcription by the accumulation of abnormal proteins when these metabolic processes are disturbed. Recent works suggest the induction of heat-shock proteins by the inhibiton of proteasome. To elucidate the mechanism of this induction, we examined the activation of heat-shock transcription factors by proteasome inhibitors in avian cells. Activation of the two heat-shock-inducible factors, HSF1 and HSF3, was produced by the treatment of cells with proteasome inhibitors. This activation was not produced by treatment with various other protease inhibitors. The HSF activation by proteasome inhibitors was completely blocked in the presence of the protein synthesis inhibitor cycloheximide. Unexpectedly, the development-related factor HSF2 was also activated by proteasome inhibitors, with an increase in its protein level. These results suggest that the ubiqutin-proteasome pathway may regulate all of the three HSFs by controlling the level of some regulatory factor for HSF or HSF itself, as well as controlling abnormal proteins.Keywords : heat-shock ; heat-shock transcription factor; proteasome; stress response ; transcription.Heat-shock proteins (Hsps) and molecular chaperones are in-In the present study, we examined the activation of the three HSFs in avian cells by proteasome inhibitors. We found that all volved in many cellular metabolic processes including protein the three HSFs were activated and, consequently, all the major synthesis, folding/assembly, membrane translocation and degraHsps were fully induced. We discuss the activation mechanisms dation in normally growing cells [19,24]. Under stress condiof these HSFs. tions, abnormal proteins increase, and this may cause the induction of Hsps. Recent works have shown that the inhibition of the ubiquitin-proteasome pathway caused the induction of cytosolic Hsp70 and glucose-regulated proteins (Grps) in the endoplasmic EXPERIMENTAL PROCEDURES reticulum [4,14,16,37]. However, little is known about the Materials. Carbobenzoxy-L-leucyl-L-leucyl-L-leucinal mechanism of this induction.(MG132), calpain inhibitor carbobenzoxy-L-leucyl-L-leucinal The expression of Hsps is regulated mainly at the level of (MG135), and E64 were purchased from the Peptide Institute transcription by heat-shock transcription factors (HSFs). In ver-and lactacystin from Kyowa Medics. Other protease inhibitors tebrates, four HSF genes (HSF1Ϫ4) have been isolated and were obtained from Nacalai Tesque. characterized [21,23,26, 29, 30]. HSF1 is a major factor that Cell culture. The chicken erythroblastic cell line HD6 [3] is activated by heat-shock and by exposure to other environmen-was maintained in HD6 medium [434 ml Dulbecco's modified tal or physiological stresses [1,27]. In avian cells, HSF3 is an-eagle medium (DMEM), 40 ml fetal calf serum, 10 ml chicken other heat-shock-responsive factor which is co-expre...

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HSF4, a New Member of the Human Heat Shock Factor Family Which Lacks Properties of a Transcriptional Activator

Cited by 311 publications

References 41 publications

Determination of the consensus binding sequence for the purified embryonic heat shock factor 2

Determination of the consensus binding sequence for the purified embryonic heat shock factor 2

HSP70.1 and -70.3 are required for late-phase protection induced by ischemic preconditioning of mouse hearts

Proteasome inhibition leads to the activation of all members of the heat‐shock‐factor family

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