hsf-1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003700 DNA-binding transcription factor activity	IBA GO_REF:0000033	ACCEPT	Summary: HSF-1 is well-established as a DNA-binding transcription factor that activates heat shock gene expression by binding to heat shock elements (HSEs) in target promoters. This function is extensively supported by multiple publications demonstrating HSF-1's transcriptional activity in both stress-dependent and stress-independent contexts (PMID:15611166, PMID:22265419, PMID:27688402, PMID:26759377). Reason: Core molecular function of HSF-1 as a transcription factor is thoroughly validated across multiple independent studies using genetic, biochemical, and molecular approaches. The IBA annotation is well-supported by phylogenetic conservation and direct experimental evidence in C. elegans. Supporting Evidence: PMID:15611166 hsf-1 encodes the C. elegans homolog of the human heat-shock factor HSF1 PMID:22265419 the activity of HSF-1 is regulated by IIS file:worm/hsf-1/hsf-1-deep-research-falcon.md model: Edison Scientific Literature
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA GO_REF:0000033	ACCEPT	Summary: HSF-1 binds to specific DNA sequences (heat shock elements) to regulate transcription by RNA polymerase II. Direct evidence from ChIP studies and DNA-binding assays supports this activity (PMID:26212459, PMID:26759377). Reason: This more specific term accurately describes HSF-1's mechanism of action as a sequence-specific DNA-binding transcription factor that regulates Pol II-dependent transcription. Supported by direct experimental evidence in C. elegans. Supporting Evidence: PMID:26759377 The transcriptional activation of ascaroside pheromone biosynthesis genes by HSF-1 was quite notable, which is not only supported by chromatin immunoprecipitation assays
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: HSF-1 localizes constitutively to the nucleus. Multiple IDA evidence from C. elegans studies using HSF-1::GFP fusion proteins confirm nuclear localization (PMID:23107491, PMID:22265419, PMID:27688402, PMID:26212459, PMID:25557666). Reason: Core cellular localization for this transcription factor. Abundantly supported by direct visualization studies in C. elegans. Supporting Evidence: PMID:23107491 Under nonstress conditions, HSF-1::GFP was found primarily in the nucleus
GO:0003677 DNA binding	IEA GO_REF:0000043	ACCEPT	Summary: HSF-1 contains a conserved DNA-binding domain and binds to heat shock elements (HSEs). This general DNA binding annotation is subsumed by the more specific annotations for sequence-specific DNA binding. Reason: While accurate, this is a parent term of the more informative sequence-specific DNA binding annotations. The IEA from UniProt keyword mapping is consistent with experimental evidence.
GO:0003700 DNA-binding transcription factor activity	IEA GO_REF:0000002	ACCEPT	Summary: Duplicate annotation from InterPro mapping. HSF-1's transcription factor activity is well-supported by experimental evidence. Reason: Consistent with IBA and IMP annotations for the same term. The InterPro HSF DNA-binding domain annotation accurately reflects HSF-1's function.
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: Duplicate nuclear localization annotation from UniProt subcellular location mapping. Consistent with multiple IDA evidence from C. elegans. Reason: Consistent with IDA and IBA annotations for nuclear localization.
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: HSF-1 is also detected in the cytoplasm. Nuclear localization is enhanced by heat shock, suggesting cytoplasmic-nuclear shuttling (PMID:22265419). Reason: Consistent with IDA evidence showing cytoplasmic localization. HSF-1's nucleocytoplasmic distribution is regulated by IIS signaling. Supporting Evidence: PMID:23107491 Under nonstress conditions, HSF-1::GFP was found primarily in the nucleus
GO:0006351 DNA-templated transcription	IEA GO_REF:0000043	ACCEPT	Summary: HSF-1 is involved in transcription as a transcription factor. This general process term is appropriate but less informative than the specific regulatory annotations. Reason: Accurate but general. HSF-1 participates in transcription by activating heat shock gene expression.
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000002	ACCEPT	Summary: HSF-1 regulates transcription of heat shock genes and other targets. This is a core function supported by extensive experimental evidence. Reason: Accurate annotation reflecting HSF-1's regulatory role in transcription. More specific child terms are also annotated with experimental evidence.
GO:0043565 sequence-specific DNA binding	IEA GO_REF:0000120	ACCEPT	Summary: HSF-1 binds specifically to heat shock elements (HSEs) containing nGAAn pentamer repeats. Direct evidence from C. elegans supports this (PMID:21510947, PMID:26212459). Reason: Accurate molecular function annotation. HSF-1 demonstrates sequence-specific DNA binding to HSE motifs. Supporting Evidence: PMID:21510947 Heat shock transcription factor (HSF), an evolutionarily conserved heat-responsive regulator, binds to heat shock elements (HSEs) comprising continuous inverted repeats of the pentamer nGAAn
GO:0005515 protein binding	IPI PMID:22265419 HSF-1 regulators DDL-1/2 link insulin-like signaling to heat...	MODIFY	Summary: HSF-1 interacts with DDL-1 as part of the DHIC complex. However, 'protein binding' is a non-informative annotation that should be replaced with more specific terms. Reason: The 'protein binding' term is too general to be informative. The interaction with DDL-1 could be better captured with a more specific term if one exists, or this annotation could be considered for removal in favor of the identical protein binding annotation. Proposed replacements: identical protein binding Supporting Evidence: PMID:22265419 DDL-1/2 negatively regulate HSF-1 activity by forming a protein complex with HSF-1
GO:0042802 identical protein binding	IPI PMID:21510947 Diversity in DNA recognition by heat shock transcription fac...	ACCEPT	Summary: HSF-1 forms homodimers and homotrimers, which is important for its DNA-binding activity. This is supported by biochemical evidence (PMID:22265419, PMID:29042483). Reason: Accurate and informative molecular function annotation describing HSF-1's self-association, which is critical for its transcriptional activation function. Supporting Evidence: PMID:22265419 DDL-1/2 negatively regulate HSF-1 activity by forming a protein complex with HSF-1 PMID:21510947 2011 Apr 14. Diversity in DNA recognition by heat shock transcription factors (HSFs) from model organisms.
GO:0010468 regulation of gene expression	NAS PMID:22265419 HSF-1 regulators DDL-1/2 link insulin-like signaling to heat...	ACCEPT	Summary: HSF-1 regulates expression of heat shock genes and other targets. This general term is appropriate but superseded by more specific annotations. Reason: Accurate but general. More specific child terms with IMP evidence are also present in the annotation set. Supporting Evidence: PMID:22265419 HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock responses and modulation of longevity.
GO:0007210 serotonin receptor signaling pathway	IMP PMID:29042483 Olfactory experience primes the heat shock transcription fac...	KEEP AS NON CORE	Summary: HSF-1 activation is enhanced by serotonin signaling, which primes HSF-1 for chaperone gene expression. This represents a regulatory input to HSF-1 rather than HSF-1 being a direct component of serotonin signaling. Reason: While HSF-1 activity is modulated by serotonin receptor signaling (via SER-1), this represents an upstream regulatory mechanism rather than a core function of HSF-1 itself. The term suggests involvement 'in' the pathway rather than being regulated by it. Supporting Evidence: PMID:25557666 Serotonin release elicited by direct optogenetic stimulation of serotonergic neurons activates HSF1 and upregulates molecular chaperones through the metabotropic serotonin receptor SER-1 PMID:29042483 Olfactory experience primes the heat shock transcription factor HSF-1 to enhance the expression of molecular chaperones in C.
GO:0016604 nuclear body	IDA PMID:29042483 Olfactory experience primes the heat shock transcription fac...	ACCEPT	Summary: HSF-1 forms nuclear stress granules upon heat shock. These are distinct subnuclear structures that partially overlap with sites of active transcription. Reason: Well-documented localization to nuclear stress granule structures following heat shock, supported by multiple studies (PMID:23107491, PMID:25557666). Supporting Evidence: PMID:23107491 Following heat shock, HSF-1::GFP rapidly and reversibly redistributed into dynamic, subnuclear structures that share many properties with human nuclear stress granules PMID:29042483 Olfactory experience primes the heat shock transcription factor HSF-1 to enhance the expression of molecular chaperones in C.
GO:0050829 defense response to Gram-negative bacterium	IMP PMID:29042483 Olfactory experience primes the heat shock transcription fac...	KEEP AS NON CORE	Summary: HSF-1 is required for defense against Gram-negative pathogens including P. aeruginosa. Multiple studies demonstrate this role (PMID:16916933, PMID:19454349). Reason: While HSF-1 is genuinely required for resistance to Gram-negative bacteria, this appears to be mediated through its regulation of chaperone genes (HSP90/daf-21, small HSPs) rather than being a direct immune function. This is a downstream physiological consequence of HSF-1's core role in proteostasis. Supporting Evidence: PMID:16916933 HSF-1 is required for C. elegans immunity against Pseudomonas aeruginosa, Salmonella enterica, Yersinia pestis, and Enterococcus faecalis PMID:29042483 Olfactory experience primes the heat shock transcription factor HSF-1 to enhance the expression of molecular chaperones in C.
GO:1990834 response to odorant	IMP PMID:29042483 Olfactory experience primes the heat shock transcription fac...	KEEP AS NON CORE	Summary: Olfactory experience with pathogen odor primes HSF-1 activity. This is part of a neuroendocrine regulation mechanism. Reason: This annotation reflects the finding that olfactory experience primes HSF-1, but this is an upstream regulatory input to HSF-1 rather than a core function. HSF-1 itself does not sense odorants; rather, the nervous system regulates HSF-1 activity in response to olfactory cues. Supporting Evidence: PMID:29042483 enhancement of chaperone gene expression required serotonin, which primed HSF-1
GO:0009408 response to heat	IMP PMID:28837599 HSF-1 is a regulator of miRNA expression in Caenorhabditis e...	ACCEPT	Summary: HSF-1 is the master regulator of the heat shock response. Multiple studies demonstrate this core function (PMID:15611166, PMID:16916933, PMID:26759377). Reason: Core biological process function of HSF-1. This is the defining role of heat shock transcription factors across all eukaryotes. Supporting Evidence: PMID:15611166 Heat-shock-induced expression of hsp-16.2 mRNA was reduced in cyl-1 mutants and virtually eliminated in hsf-1 and sup-45 mutants PMID:28837599 eCollection 2017. HSF-1 is a regulator of miRNA expression in Caenorhabditis elegans.
GO:0010628 positive regulation of gene expression	IMP PMID:28837599 HSF-1 is a regulator of miRNA expression in Caenorhabditis e...	ACCEPT	Summary: HSF-1 positively regulates expression of heat shock genes, miRNAs, and developmental genes. This is a core transcriptional activator function. Reason: Well-supported core function. HSF-1 is primarily a transcriptional activator. Supporting Evidence: PMID:28837599 HSF-1 controls miRNA expression during and independently of heat stress
GO:0010629 negative regulation of gene expression	IMP PMID:28837599 HSF-1 is a regulator of miRNA expression in Caenorhabditis e...	ACCEPT	Summary: HSF-1 also negatively regulates some genes, both directly and indirectly through miRNA regulation. Reason: Supported by miRNA-seq studies showing HSF-1-dependent regulation of miRNAs that would result in translational repression of target genes. Supporting Evidence: PMID:28837599 HSF-1 controls miRNA expression during and independently of heat stress
GO:0010628 positive regulation of gene expression	IMP PMID:28198373 Hormetic heat stress and HSF-1 induce autophagy to improve s...	ACCEPT	Summary: Duplicate annotation with different reference. HSF-1 induces expression of autophagy genes following hormetic heat stress. Reason: Consistent with other annotations showing HSF-1 as a transcriptional activator. The autophagy context adds additional biological detail. Supporting Evidence: PMID:28198373 expression of autophagy-related genes was much higher in animals overexpressing HSF-1 than in wild-type animals under basal (non-stressed) conditions
GO:0016239 positive regulation of macroautophagy	IMP PMID:28198373 Hormetic heat stress and HSF-1 induce autophagy to improve s...	KEEP AS NON CORE	Summary: HSF-1 induces autophagy following hormetic (mild) heat stress, contributing to proteostasis and improved survival. Reason: While this is a genuine HSF-1 function demonstrated by IMP evidence, it appears to be a downstream consequence of HSF-1's transcriptional program rather than a core molecular function. It represents one of the physiological outcomes of HSF-1 activation. Supporting Evidence: PMID:28198373 autophagy is induced in multiple tissues of Caenorhabditis elegans following hormetic heat stress or HSF-1 overexpression
GO:0000785 chromatin	IMP PMID:26759377 HSF-1 is involved in regulation of ascaroside pheromone bios...	ACCEPT	Summary: HSF-1 associates with chromatin at target gene promoters, as demonstrated by ChIP assays. Reason: Accurate localization annotation supported by ChIP evidence showing HSF-1 binding to chromatin at ascaroside biosynthesis gene loci. Supporting Evidence: PMID:26759377 The transcriptional activation of ascaroside pheromone biosynthesis genes by HSF-1 was quite notable, which is not only supported by chromatin immunoprecipitation assays
GO:0003682 chromatin binding	IMP PMID:26759377 HSF-1 is involved in regulation of ascaroside pheromone bios...	ACCEPT	Summary: HSF-1 binds to chromatin at target gene promoters. This is related to its function as a DNA-binding transcription factor. Reason: Accurate molecular function annotation supported by ChIP evidence. Supporting Evidence: PMID:26759377 The transcriptional activation of ascaroside pheromone biosynthesis genes by HSF-1 was quite notable, which is not only supported by chromatin immunoprecipitation assays
GO:0003700 DNA-binding transcription factor activity	IMP PMID:26759377 HSF-1 is involved in regulation of ascaroside pheromone bios...	ACCEPT	Summary: Another IMP annotation for HSF-1's transcription factor activity, this time in the context of ascaroside biosynthesis gene regulation. Reason: Consistent with other annotations. Strong experimental support for this core function. Supporting Evidence: PMID:26759377 HSF-1 is involved in regulation of ascaroside pheromone biosynthesis by heat stress in Caenorhabditis elegans.
GO:0009408 response to heat	IMP PMID:26759377 HSF-1 is involved in regulation of ascaroside pheromone bios...	ACCEPT	Summary: Duplicate annotation for response to heat with different reference. This study links heat stress to ascaroside pheromone biosynthesis via HSF-1. Reason: Core function with additional experimental evidence. Supporting Evidence: PMID:26759377 HSF-1 is involved in regulation of ascaroside pheromone biosynthesis by heat stress in Caenorhabditis elegans.
GO:0010623 programmed cell death involved in cell development	IMP PMID:26952214 HSF-1 activates the ubiquitin proteasome system to promote n...	KEEP AS NON CORE	Summary: HSF-1 promotes linker cell death (LCD), a non-apoptotic developmental cell death process. This is a heat shock-independent developmental function. Reason: This is a genuine developmental function of HSF-1 that is independent of its stress response role. While important, it represents a specialized developmental context rather than the core molecular function of HSF-1. Supporting Evidence: PMID:26952214 HSF-1 activates the ubiquitin proteasome system to promote non-apoptotic developmental cell death
GO:0010623 programmed cell death involved in cell development	IGI PMID:26952214 HSF-1 activates the ubiquitin proteasome system to promote n...	KEEP AS NON CORE	Summary: Duplicate annotation with IGI evidence showing genetic interaction with other LCD regulators. Reason: Consistent with IMP annotation. The IGI evidence strengthens the case for HSF-1's role in LCD. Supporting Evidence: PMID:26952214 HSF-1 activates the ubiquitin proteasome system to promote non-apoptotic developmental cell death in C.
GO:0010628 positive regulation of gene expression	IMP PMID:26952214 HSF-1 activates the ubiquitin proteasome system to promote n...	ACCEPT	Summary: HSF-1 activates expression of let-70 (E2 ubiquitin ligase) and ubiquitin genes during linker cell death. Reason: Core transcriptional activator function in a developmental context. Supporting Evidence: PMID:26952214 let-70, encoding a conserved E2 ubiquitin-conjugating enzyme, is an important transcriptional target of this pro-death developmental activity of HSF-1
GO:0032000 positive regulation of fatty acid beta-oxidation	IMP PMID:26759377 HSF-1 is involved in regulation of ascaroside pheromone bios...	KEEP AS NON CORE	Summary: HSF-1 activates transcription of peroxisomal fatty acid beta-oxidation genes in response to heat stress, contributing to ascaroside pheromone biosynthesis. Reason: This is an indirect effect of HSF-1's transcriptional activation of metabolic genes rather than a core function. It represents a specific metabolic outcome of HSF-1 activation. Supporting Evidence: PMID:26759377 the heat-shock transcription factor HSF-1 can mediate enhanced ascaroside pheromone biosynthesis in response to heat stress by activating the peroxisomal fatty acid beta-oxidation genes
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:26759377 HSF-1 is involved in regulation of ascaroside pheromone bios...	ACCEPT	Summary: HSF-1 positively regulates Pol II-dependent transcription of target genes. Reason: Core molecular function of HSF-1 as a transcriptional activator of Pol II-dependent transcription. Supporting Evidence: PMID:26759377 HSF-1 is involved in regulation of ascaroside pheromone biosynthesis by heat stress in Caenorhabditis elegans.
GO:1904070 ascaroside biosynthetic process	IMP PMID:26759377 HSF-1 is involved in regulation of ascaroside pheromone bios...	KEEP AS NON CORE	Summary: HSF-1 regulates ascaroside pheromone biosynthesis by activating genes in this pathway. Reason: This is a specific biological outcome of HSF-1 transcriptional activity rather than a core function. The effect is mediated indirectly through activation of biosynthetic genes. Supporting Evidence: PMID:26759377 production of ascarosides is stimulated by heat stress, resulting in enhanced dauer formation
GO:1905911 positive regulation of dauer entry	IMP PMID:26759377 HSF-1 is involved in regulation of ascaroside pheromone bios...	KEEP AS NON CORE	Summary: HSF-1 promotes dauer entry by regulating ascaroside pheromone production. This is an indirect effect mediated through transcriptional activation. Reason: Indirect effect of HSF-1 on dauer formation through regulation of pheromone biosynthesis genes rather than a direct developmental function. Supporting Evidence: PMID:26759377 the dauer formation rate was significantly increased by the ascaroside pheromone extracts from N2 wild-type but not from hsf-1(sy441) mutant animals
GO:0009408 response to heat	IMP PMID:16916933 Heat-shock transcription factor (HSF)-1 pathway required for...	ACCEPT	Summary: Another IMP annotation for response to heat with immunity context. Reason: Core function with multiple lines of experimental evidence. Supporting Evidence: PMID:16916933 Heat-shock transcription factor (HSF)-1 pathway required for Caenorhabditis elegans immunity.
GO:0050829 defense response to Gram-negative bacterium	IMP PMID:16916933 Heat-shock transcription factor (HSF)-1 pathway required for...	KEEP AS NON CORE	Summary: HSF-1 is required for defense against P. aeruginosa and other Gram-negative pathogens. Reason: Consistent with other annotations. Immune defense is likely an indirect effect of HSF-1's chaperone gene regulation. Supporting Evidence: PMID:16916933 HSF-1 is required for C. elegans immunity against Pseudomonas aeruginosa, Salmonella enterica, Yersinia pestis, and Enterococcus faecalis
GO:0050830 defense response to Gram-positive bacterium	IMP PMID:16916933 Heat-shock transcription factor (HSF)-1 pathway required for...	KEEP AS NON CORE	Summary: HSF-1 is also required for defense against Gram-positive pathogens like E. faecalis. Reason: Similar to Gram-negative defense, this is likely mediated through HSF-1's regulation of chaperone genes rather than being a direct immune function. Supporting Evidence: PMID:16916933 HSF-1 is required for C. elegans immunity against Pseudomonas aeruginosa, Salmonella enterica, Yersinia pestis, and Enterococcus faecalis
GO:0012501 programmed cell death	IGI PMID:27472063 Transcriptional control of non-apoptotic developmental cell ...	KEEP AS NON CORE	Summary: HSF-1 participates in non-apoptotic programmed cell death (linker cell death). This parent term is less specific than the developmental cell death annotation. Reason: Accurate but less specific than GO:0010623. Represents developmental role of HSF-1. Supporting Evidence: PMID:27472063 Although HSF-1 functions to protect cells from stress in many settings by inducing expression of protein folding chaperones, it promotes LCD by inducing expression of the conserved E2 ubiquitin-conjugating enzyme LET-70/UBE2D2
GO:0002119 nematode larval development	IMP PMID:27688402 E2F coregulates an essential HSF developmental program that ...	KEEP AS NON CORE	Summary: HSF-1 has a developmental role in larval development that is independent of heat shock, acting with E2F/efl-1. Reason: This developmental function is independent of the canonical heat shock response and represents a specialized context-dependent role of HSF-1. Supporting Evidence: PMID:27688402 E2F coregulates an essential HSF developmental program that is distinct from the heat-shock response
GO:0005634 nucleus	IDA PMID:22265419 HSF-1 regulators DDL-1/2 link insulin-like signaling to heat...	ACCEPT	Summary: Direct visualization of HSF-1::GFP showing nuclear localization. Reason: Core localization annotation with direct experimental evidence. Supporting Evidence: PMID:22265419 HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock responses and modulation of longevity.
GO:0005634 nucleus	IDA PMID:27688402 E2F coregulates an essential HSF developmental program that ...	ACCEPT	Summary: Duplicate IDA annotation for nuclear localization. Reason: Consistent with other nuclear localization annotations. Supporting Evidence: PMID:27688402 HSF-1 is essential for C. elegans larval development
GO:0005737 cytoplasm	IDA PMID:22265419 HSF-1 regulators DDL-1/2 link insulin-like signaling to heat...	ACCEPT	Summary: Direct visualization showing HSF-1 cytoplasmic localization, which is enhanced when IIS signaling inhibits nuclear translocation. Reason: Accurate localization annotation reflecting the nucleocytoplasmic distribution of HSF-1. Supporting Evidence: PMID:22265419 DDL-1/2 negatively regulate HSF-1 activity by forming a protein complex with HSF-1
GO:0005634 nucleus	IDA PMID:26212459 Repression of the Heat Shock Response Is a Programmed Event ...	ACCEPT	Summary: Nuclear localization in context of chromatin binding studies. Reason: Consistent with other nuclear localization annotations. Supporting Evidence: PMID:26212459 2015 Jul 23. Repression of the Heat Shock Response Is a Programmed Event at the Onset of Reproduction.
GO:1990837 sequence-specific double-stranded DNA binding	IDA PMID:26212459 Repression of the Heat Shock Response Is a Programmed Event ...	ACCEPT	Summary: HSF-1 binds specifically to heat shock elements in double-stranded DNA. Reason: Core molecular function annotation with direct experimental evidence from ChIP studies. Supporting Evidence: PMID:26212459 This results in a repressed chromatin state that interferes with HSF-1 binding and suppresses transcription initiation in response to stress
GO:1990841 promoter-specific chromatin binding	IDA PMID:26212459 Repression of the Heat Shock Response Is a Programmed Event ...	ACCEPT	Summary: HSF-1 binds to chromatin at specific promoter regions containing HSE elements. Reason: Accurate and specific molecular function annotation describing HSF-1's mechanism of action at target gene promoters. Supporting Evidence: PMID:26212459 2015 Jul 23. Repression of the Heat Shock Response Is a Programmed Event at the Onset of Reproduction.
GO:0005634 nucleus	IDA PMID:25557666 Neuronal serotonin release triggers the heat shock response ...	ACCEPT	Summary: Nuclear localization in context of serotonin-mediated HSF-1 activation studies. Reason: Consistent with other nuclear localization annotations. Supporting Evidence: PMID:25557666 Serotonin release elicited by direct optogenetic stimulation of serotonergic neurons activates HSF1
GO:0097165 nuclear stress granule	IDA PMID:25557666 Neuronal serotonin release triggers the heat shock response ...	ACCEPT	Summary: HSF-1 localizes to nuclear stress granules following heat shock or serotonin signaling. Reason: Specific and informative localization annotation with direct experimental evidence. Supporting Evidence: PMID:23107491 Following heat shock, HSF-1::GFP rapidly and reversibly redistributed into dynamic, subnuclear structures that share many properties with human nuclear stress granules PMID:25557666 2014 Dec 31. Neuronal serotonin release triggers the heat shock response in C.
GO:0035966 response to topologically incorrect protein	IMP PMID:23335331 A novel interaction between aging and ER overload in a prote...	ACCEPT	Summary: HSF-1 is required for the response to misfolded/aggregated proteins (proteotoxic stress), as shown in a neuroserpin aggregation disease model. Reason: Core function of HSF-1 in proteostasis. The heat shock response fundamentally addresses protein folding stress. Supporting Evidence: PMID:23335331 Thus, we find that perturbations of proteostasis through impairment of the heat shock response or altered UPR signaling enhance neuroserpin accumulation in vivo
GO:0035966 response to topologically incorrect protein	IGI PMID:23335331 A novel interaction between aging and ER overload in a prote...	ACCEPT	Summary: Duplicate annotation with IGI evidence from genetic interaction studies. Reason: Consistent with IMP annotation. Strengthens evidence for proteostasis role. Supporting Evidence: PMID:23335331 Jan 18. A novel interaction between aging and ER overload in a protein conformational dementia.
GO:0035966 response to topologically incorrect protein	IMP PMID:19165329 An ALS-linked mutant SOD1 produces a locomotor defect associ...	ACCEPT	Summary: HSF-1 is involved in response to misfolded SOD1 in an ALS model. Reason: Further support for HSF-1's role in proteostasis and response to protein aggregation. Supporting Evidence: PMID:19165329 For example, heat shock factor 1 (HSF1), which transcriptionally regulates a number of stress components [44], registered very strongly in the RNAi screen in increasing aggregate formation
GO:0005516 calmodulin binding	IPI PMID:17854888 Ca(2+)/Calmodulin-binding proteins from the C. elegans prote...	UNDECIDED	Summary: HSF-1 was identified as a Ca2+/calmodulin-binding protein in a proteome-wide screen. Reason: While the interaction was identified by a validated method (mRNA-display), the functional significance of calmodulin binding for HSF-1 activity is not clear from the study. More investigation is needed to determine if this represents a physiologically relevant regulatory interaction. Supporting Evidence: PMID:17854888 identification of 9 known and 47 previously uncharacterized Ca(2+)-dependent CaM-binding proteins from the adult worm proteome
GO:0045087 innate immune response	IMP PMID:19454349 Conditioning protects C. elegans from lethal effects of ente...	KEEP AS NON CORE	Summary: HSF-1 is required for innate immunity, particularly in the context of conditioning against pathogens. Reason: This is likely an indirect effect of HSF-1's chaperone gene regulation on immune function rather than a direct immune signaling role. Supporting Evidence: PMID:19454349 Conditioning protects C. elegans from lethal effects of enteropathogenic E. coli by activating genes that regulate lifespan and innate immunity
GO:0050829 defense response to Gram-negative bacterium	IMP PMID:19454349 Conditioning protects C. elegans from lethal effects of ente...	KEEP AS NON CORE	Summary: Duplicate annotation in immunity context (conditioning study). Reason: Consistent with other immune defense annotations. Supporting Evidence: PMID:19454349 Conditioning protects C.
GO:0003700 DNA-binding transcription factor activity	ISS PMID:15611166 The L-type cyclin CYL-1 and the heat-shock-factor HSF-1 are ...	ACCEPT	Summary: ISS annotation based on homology to human HSF1. Reason: Consistent with IBA, IMP, and IEA annotations. The homology inference is well-supported by experimental evidence in C. elegans. Supporting Evidence: PMID:15611166 The L-type cyclin CYL-1 and the heat-shock-factor HSF-1 are required for heat-shock-induced protein expression in Caenorhabditis elegans.
GO:0005634 nucleus	ISS PMID:15611166 The L-type cyclin CYL-1 and the heat-shock-factor HSF-1 are ...	ACCEPT	Summary: ISS annotation for nuclear localization based on homology. Reason: Consistent with IDA annotations from C. elegans studies. Supporting Evidence: PMID:15611166 The L-type cyclin CYL-1 and the heat-shock-factor HSF-1 are required for heat-shock-induced protein expression in Caenorhabditis elegans.
GO:0009408 response to heat	IMP PMID:15611166 The L-type cyclin CYL-1 and the heat-shock-factor HSF-1 are ...	ACCEPT	Summary: IMP evidence for heat shock response from the foundational hsf-1 characterization study. Reason: Core function with strong experimental evidence. Supporting Evidence: PMID:15611166 Heat-shock-induced expression of hsp-16.2 mRNA was reduced in cyl-1 mutants and virtually eliminated in hsf-1 and sup-45 mutants
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:15611166 The L-type cyclin CYL-1 and the heat-shock-factor HSF-1 are ...	ACCEPT	Summary: HSF-1 activates Pol II-dependent transcription of heat shock genes. Reason: Core molecular function with experimental evidence. Supporting Evidence: PMID:15611166 The L-type cyclin CYL-1 and the heat-shock-factor HSF-1 are required for heat-shock-induced protein expression in Caenorhabditis elegans.
GO:0008340 determination of adult lifespan	IMP PMID:14668486 Regulation of longevity in Caenorhabditis elegans by heat sh...	ACCEPT	Summary: HSF-1 is required for lifespan extension in IIS pathway mutants. This is a key finding linking stress response to aging. Reason: Well-documented role of HSF-1 in lifespan regulation. The connection between proteostasis/stress response and longevity is a core aspect of HSF-1 biology. Supporting Evidence: PMID:14668486 Down-regulation of hsf-1 by RNA interference suppressed longevity of mutants in an insulin-like signaling (ILS) pathway
GO:0008340 determination of adult lifespan	IGI PMID:14668486 Regulation of longevity in Caenorhabditis elegans by heat sh...	ACCEPT	Summary: Duplicate annotation with IGI evidence from genetic interaction studies with IIS pathway components. Reason: Strengthens the case for HSF-1's role in lifespan determination. Supporting Evidence: PMID:14668486 Dec 10. Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones.
GO:0040024 dauer larval development	IGI PMID:14668486 Regulation of longevity in Caenorhabditis elegans by heat sh...	KEEP AS NON CORE	Summary: HSF-1 is required for temperature-induced dauer formation in IIS mutants. Reason: This developmental role is related to HSF-1's function in stress response but represents a specific developmental context. Supporting Evidence: PMID:14668486 hsf-1 was also required for temperature-induced dauer larvae formation in an ILS mutant
GO:0005634 nucleus	IDA PMID:23107491 Caenorhabditis elegans HSF-1 is an essential nuclear protein...	ACCEPT	Summary: Foundational study showing constitutive nuclear localization of HSF-1::GFP. Reason: Core localization with strong direct evidence. Supporting Evidence: PMID:23107491 Under nonstress conditions, HSF-1::GFP was found primarily in the nucleus
GO:0097165 nuclear stress granule	IDA PMID:23107491 Caenorhabditis elegans HSF-1 is an essential nuclear protein...	ACCEPT	Summary: Detailed characterization of HSF-1 nuclear stress granules following heat shock. Reason: Well-documented localization with functional significance for HSF-1 transcriptional activity. Supporting Evidence: PMID:23107491 Following heat shock, HSF-1::GFP rapidly and reversibly redistributed into dynamic, subnuclear structures that share many properties with human nuclear stress granules

Gene Description

Existing Annotations Review

Core Functions

HSF-1 is the master transcriptional regulator of the heat shock response, functioning as a sequence-specific DNA-binding transcription factor that binds to heat shock elements (HSEs) containing inverted nGAAn pentamer repeats.

HSF-1 binds to heat shock elements (HSEs) in the promoters of heat shock genes and other target genes to activate transcription in response to stress.

HSF-1 forms homodimers and homotrimers, which is essential for its DNA-binding and transcriptional activation activity.

References

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Falcon

📚 Additional Documentation

Bioreason Rl Predictions

Bioreason Rl Review

Curation Executive Summary

Hsf1 Annotation Review

Hsf1 Annotation Summary Table

Index

Key Evidence Quotes

Readme Curation

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