Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10192)

Regulator Name	Heat shock factor protein 1 (HSF1)
Synonyms	HSTF1; Heat shock transcription factor 1 Click to Show/Hide
Gene Name	HSF1
Gene ID	3297
Regulator Type	Protein coding
Uniprot ID	Q00613
Sequence	MDLPVGPGAAGPSNVPAFLTKLWTLVSDPDTDALICWSPSGNSFHVFDQGQFAKEVLPKY FKHNNMASFVRQLNMYGFRKVVHIEQGGLVKPERDDTEFQHPCFLRGQEQLLENIKRKVT SVSTLKSEDIKIRQDSVTKLLTDVQLMKGKQECMDSKLLAMKHENEALWREVASLRQKHA QQQKVVNKLIQFLISLVQSNRILGVKRKIPLMLNDSGSAHSMPKYSRQFSLEHVHGSGPY SAPSPAYSSSSLYAPDAVASSGPIISDITELAPASPMASPGGSIDERPLSSSPLVRVKEE PPSPPQSPRVEEASPGRPSSVDTLLSPTALIDSILRESEPAPASVTALTDARGHTDTEGR PPSPPPTSTPEKCLSVACLDKNELSDHLDAMDSNLDNLQTMLSSHGFSVDTSALLDLFSP SVTVPDMSLPDLDSSLASIQELLSPQEPPRPPEAENSSPDSGKQLVHYTAQPLFLLDPGS VDTGSNDLPVLFELGEGSYFSEGDGFAEDPTISLLTGSEPPKAKDPTVS Click to Show/Hide
Family	HSF family
Function	Functions as a stress-inducible and DNA-binding transcription factor that plays a central role in the transcriptional activation of the heat shock response (HSR), leading to the expression of a large class of molecular chaperones, heat shock proteins (HSPs), that protect cells from cellular insult damage. In unstressed cells, is present in a HSP90-containing multichaperone complex that maintains it in a non-DNA-binding inactivated monomeric form. Upon exposure to heat and other stress stimuli, undergoes homotrimerization and activates HSP gene transcription through binding to site-specific heat shock elements (HSEs) present in the promoter regions of HSP genes. Upon heat shock stress, forms a chromatin-associated complex with TTC5/STRAP and p300/EP300 to stimulate HSR transcription, therefore increasing cell survival. Activation is reversible, and during the attenuation and recovery phase period of the HSR, returns to its unactivated form. Binds to inverted 5'-NGAAN-3' pentamer DNA sequences. Binds to chromatin at heat shock gene promoters. Activates transcription of transcription factor FOXR1 which in turn activates transcription of the heat shock chaperones HSPA1A and HSPA6 and the antioxidant NADPH-dependent reductase DHRS2. Also serves several other functions independently of its transcriptional activity. Involved in the repression of Ras-induced transcriptional activation of the c-fos gene in heat-stressed cells. Positively regulates pre-mRNA 3'-end processing and polyadenylation of HSP70 mRNA upon heat-stressed cells in a symplekin (SYMPK)-dependent manner. Plays a role in nuclear export of stress- induced HSP70 mRNA. Plays a role in the regulation of mitotic progression. Also plays a role as a negative regulator of non-homologous end joining (NHEJ) repair activity in a DNA damage-dependent manner. Involved in stress-induced cancer cell proliferation in a IER5-dependent manner. Click to Show/Hide
HGNC ID	HGNC:5224
KEGG ID	hsa:3297

Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)

HSF1 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).

Browse Target

Browse Disease

Browse Drug

Heat shock protein beta-1 (HSPB1) [Suppressor; Marker]

Target Info

In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator				[1]
Target for Ferroptosis	Marker/Suppressor
Responsed Disease	Cervical cancer		ICD-11: 2C77	Disease Info
Responsed Drug	Erastin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	U2OS cells	Osteosarcoma	Homo sapiens	CVCL_0042
	LNCaP cells	Prostate carcinoma	Homo sapiens	CVCL_0395
In Vivo Model	Indicated HeLa cells were subcutaneously injected into the dorsal flanks right of the midline in SCID mice (weight ~20 g). At day seven, mice were injected with erastin (20 mg/kg/ i.v., twice daily every other day) with or without KRIBB3 (50 mg/kg/ i.p., once daily every other day) for two weeks. Erastin was dissolved in vehicle (2% DMSO and 98% phosphate buffered saline) and prepared by Ultrasonic Cleaner (Fisher Scientific). A final volume of 300 ul erastin was applied through the tail vein. The Rodent Tail Vein Catheter (Braintree Scientific, MTV#1) were used to perform injection. Click to Show/Hide
Response regulation	Erastin, a specific ferroptosis-inducing compound, stimulates heat shock factor 1 ( HSF1)-dependent HSPB1 expression in endocervical adenocarcinoma cells. Knockdown of HSF1 and HSPB1 enhances erastin-induced ferroptosis, whereas heat shock pretreatment and overexpression of HSPB1 inhibits erastin-induced ferroptosis.
Experiment 2 Reporting the Ferroptosis Target of This Regulator				[1]
Target for Ferroptosis	Marker/Suppressor
Responsed Disease	Cervical cancer		ICD-11: 2C77	Disease Info
Responsed Drug	Erastin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	U2OS cells	Osteosarcoma	Homo sapiens	CVCL_0042
	LNCaP cells	Prostate carcinoma	Homo sapiens	CVCL_0395
In Vivo Model	Indicated HeLa cells were subcutaneously injected into the dorsal flanks right of the midline in SCID mice (weight ~20 g). At day seven, mice were injected with erastin (20 mg/kg/ i.v., twice daily every other day) with or without KRIBB3 (50 mg/kg/ i.p., once daily every other day) for two weeks. Erastin was dissolved in vehicle (2% DMSO and 98% phosphate buffered saline) and prepared by Ultrasonic Cleaner (Fisher Scientific). A final volume of 300 ul erastin was applied through the tail vein. The Rodent Tail Vein Catheter (Braintree Scientific, MTV#1) were used to perform injection. Click to Show/Hide
Response regulation	Erastin, a specific ferroptosis-inducing compound, stimulates heat shock factor 1 (HSF1)-dependent HSPB1 expression in endocervical adenocarcinoma cells. Knockdown of HSF1 and HSPB1 enhances erastin-induced ferroptosis, whereas heat shock pretreatment and overexpression of HSPB1 inhibits erastin-induced ferroptosis.

Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]

Target Info

In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator				[2]
Target for Ferroptosis	Suppressor
Responsed Disease	Health		ICD-11: N.A.	Disease Info
Responsed Drug	Palmitic acid		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
In Vivo Model	Hsf1 and Hsf1+/+-/- mice were kindly given as a present by Dr. Ivor J. Benjamin (Froedtert & Medical College of Wisconsin, Milwaukee, WI, USA). Sex-matched Hsf1-/- mice and Hsf1 littermates were used at 16-20 weeks old. Each mouse was injected intraperitoneally with 2.5 umol PA (dissolved in 0.5 mL 10% BSA) or an equal volume of BSA twice daily for 7 days. Click to Show/Hide
Response regulation	Palmitic acid (PA) decreased the protein expression levels of both heat shock factor 1 (HSF1) and glutathione peroxidase 4 (GPX4) in a dose- and time-dependent manner, which were restored by different ferroptosis inhibitors. Altogether, HSF1 may function as a key defender against PA-induced ferroptosis in cardiomyocytes by maintaining cellular iron homeostasis and GPX4 expression.

Cervical cancer [ICD-11: 2C77]

Disease Info

In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[1]
Target Regulator	Heat shock factor protein 1 (HSF1)		Protein coding	Regulator Info
Responsed Drug	Erastin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	U2OS cells	Osteosarcoma	Homo sapiens	CVCL_0042
	LNCaP cells	Prostate carcinoma	Homo sapiens	CVCL_0395
In Vivo Model	Indicated HeLa cells were subcutaneously injected into the dorsal flanks right of the midline in SCID mice (weight ~20 g). At day seven, mice were injected with erastin (20 mg/kg/ i.v., twice daily every other day) with or without KRIBB3 (50 mg/kg/ i.p., once daily every other day) for two weeks. Erastin was dissolved in vehicle (2% DMSO and 98% phosphate buffered saline) and prepared by Ultrasonic Cleaner (Fisher Scientific). A final volume of 300 ul erastin was applied through the tail vein. The Rodent Tail Vein Catheter (Braintree Scientific, MTV#1) were used to perform injection. Click to Show/Hide
Response regulation	Erastin, a specific ferroptosis-inducing compound, stimulates heat shock factor 1 ( HSF1)-dependent HSPB1 expression in endocervical adenocarcinoma cells. Knockdown of HSF1 and HSPB1 enhances erastin-induced ferroptosis, whereas heat shock pretreatment and overexpression of HSPB1 inhibits erastin-induced ferroptosis.
Experiment 2 Reporting the Ferroptosis-centered Disease Response				[1]
Target Regulator	Heat shock factor protein 1 (HSF1)		Protein coding	Regulator Info
Responsed Drug	Erastin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	U2OS cells	Osteosarcoma	Homo sapiens	CVCL_0042
	LNCaP cells	Prostate carcinoma	Homo sapiens	CVCL_0395
In Vivo Model	Indicated HeLa cells were subcutaneously injected into the dorsal flanks right of the midline in SCID mice (weight ~20 g). At day seven, mice were injected with erastin (20 mg/kg/ i.v., twice daily every other day) with or without KRIBB3 (50 mg/kg/ i.p., once daily every other day) for two weeks. Erastin was dissolved in vehicle (2% DMSO and 98% phosphate buffered saline) and prepared by Ultrasonic Cleaner (Fisher Scientific). A final volume of 300 ul erastin was applied through the tail vein. The Rodent Tail Vein Catheter (Braintree Scientific, MTV#1) were used to perform injection. Click to Show/Hide
Response regulation	Erastin, a specific ferroptosis-inducing compound, stimulates heat shock factor 1 (HSF1)-dependent HSPB1 expression in endocervical adenocarcinoma cells. Knockdown of HSF1 and HSPB1 enhances erastin-induced ferroptosis, whereas heat shock pretreatment and overexpression of HSPB1 inhibits erastin-induced ferroptosis.

Health [ICD-11: N.A.]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[2]
Target Regulator	Heat shock factor protein 1 (HSF1)		Protein coding	Regulator Info
Responsed Drug	Palmitic acid		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
In Vivo Model	Hsf1 and Hsf1+/+-/- mice were kindly given as a present by Dr. Ivor J. Benjamin (Froedtert & Medical College of Wisconsin, Milwaukee, WI, USA). Sex-matched Hsf1-/- mice and Hsf1 littermates were used at 16-20 weeks old. Each mouse was injected intraperitoneally with 2.5 umol PA (dissolved in 0.5 mL 10% BSA) or an equal volume of BSA twice daily for 7 days. Click to Show/Hide
Response regulation	Palmitic acid (PA) decreased the protein expression levels of both heat shock factor 1 (HSF1) and glutathione peroxidase 4 (GPX4) in a dose- and time-dependent manner, which were restored by different ferroptosis inhibitors. Altogether, HSF1 may function as a key defender against PA-induced ferroptosis in cardiomyocytes by maintaining cellular iron homeostasis and GPX4 expression.

Erastin [Investigative]

Drug Info

In total 2 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[1]
Drug for Ferroptosis	Suppressor
Response Target	Heat shock protein beta-1 (HSPB1)		Suppressor; Marker	Target Info
Responsed Disease	Cervical cancer		ICD-11: 2C77	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	U2OS cells	Osteosarcoma	Homo sapiens	CVCL_0042
	LNCaP cells	Prostate carcinoma	Homo sapiens	CVCL_0395
In Vivo Model	Indicated HeLa cells were subcutaneously injected into the dorsal flanks right of the midline in SCID mice (weight ~20 g). At day seven, mice were injected with erastin (20 mg/kg/ i.v., twice daily every other day) with or without KRIBB3 (50 mg/kg/ i.p., once daily every other day) for two weeks. Erastin was dissolved in vehicle (2% DMSO and 98% phosphate buffered saline) and prepared by Ultrasonic Cleaner (Fisher Scientific). A final volume of 300 ul erastin was applied through the tail vein. The Rodent Tail Vein Catheter (Braintree Scientific, MTV#1) were used to perform injection. Click to Show/Hide
Response regulation	Erastin, a specific ferroptosis-inducing compound, stimulates heat shock factor 1 ( HSF1)-dependent HSPB1 expression in endocervical adenocarcinoma cells. Knockdown of HSF1 and HSPB1 enhances erastin-induced ferroptosis, whereas heat shock pretreatment and overexpression of HSPB1 inhibits erastin-induced ferroptosis.
Experiment 2 Reporting the Ferroptosis-centered Drug Response				[1]
Drug for Ferroptosis	Suppressor
Response Target	Heat shock protein beta-1 (HSPB1)		Suppressor; Marker	Target Info
Responsed Disease	Cervical cancer		ICD-11: 2C77	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	U2OS cells	Osteosarcoma	Homo sapiens	CVCL_0042
	LNCaP cells	Prostate carcinoma	Homo sapiens	CVCL_0395
In Vivo Model	Indicated HeLa cells were subcutaneously injected into the dorsal flanks right of the midline in SCID mice (weight ~20 g). At day seven, mice were injected with erastin (20 mg/kg/ i.v., twice daily every other day) with or without KRIBB3 (50 mg/kg/ i.p., once daily every other day) for two weeks. Erastin was dissolved in vehicle (2% DMSO and 98% phosphate buffered saline) and prepared by Ultrasonic Cleaner (Fisher Scientific). A final volume of 300 ul erastin was applied through the tail vein. The Rodent Tail Vein Catheter (Braintree Scientific, MTV#1) were used to perform injection. Click to Show/Hide
Response regulation	Erastin, a specific ferroptosis-inducing compound, stimulates heat shock factor 1 (HSF1)-dependent HSPB1 expression in endocervical adenocarcinoma cells. Knockdown of HSF1 and HSPB1 enhances erastin-induced ferroptosis, whereas heat shock pretreatment and overexpression of HSPB1 inhibits erastin-induced ferroptosis.

Palmitic acid [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[2]
Drug for Ferroptosis	Inducer
Response Target	Phospholipid hydroperoxide glutathione peroxidase (GPX4)		Suppressor	Target Info
Responsed Disease	Health		ICD-11: N.A.	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
In Vivo Model	Hsf1 and Hsf1+/+-/- mice were kindly given as a present by Dr. Ivor J. Benjamin (Froedtert & Medical College of Wisconsin, Milwaukee, WI, USA). Sex-matched Hsf1-/- mice and Hsf1 littermates were used at 16-20 weeks old. Each mouse was injected intraperitoneally with 2.5 umol PA (dissolved in 0.5 mL 10% BSA) or an equal volume of BSA twice daily for 7 days. Click to Show/Hide
Response regulation	Palmitic acid (PA) decreased the protein expression levels of both heat shock factor 1 (HSF1) and glutathione peroxidase 4 (GPX4) in a dose- and time-dependent manner, which were restored by different ferroptosis inhibitors. Altogether, HSF1 may function as a key defender against PA-induced ferroptosis in cardiomyocytes by maintaining cellular iron homeostasis and GPX4 expression.

References

Ref 1	HSPB1 as a novel regulator of ferroptotic cancer cell death. Oncogene. 2015 Nov 5;34(45):5617-25. doi: 10.1038/onc.2015.32. Epub 2015 Mar 2.
Ref 2	HSF1 functions as a key defender against palmitic acid-induced ferroptosis in cardiomyocytes. J Mol Cell Cardiol. 2021 Jan;150:65-76. doi: 10.1016/j.yjmcc.2020.10.010. Epub 2020 Oct 22.

Ferroptosis Regulator Information

About FERREG

Visitor Map

Correspondence

Prof. Shuiping Liu