Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10429)
Regulator Name Heat shock protein 105 kDa (HSPH1)
Synonyms
HSP105; HSP110; KIAA0201; Antigen NY-CO-25; Heat shock 110 kDa protein
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Gene Name HSPH1
Gene ID 10808
Regulator Type Protein coding
Uniprot ID Q92598
Sequence
MSVVGLDVGSQSCYIAVARAGGIETIANEFSDRCTPSVISFGSKNRTIGVAAKNQQITHA
NNTVSNFKRFHGRAFNDPFIQKEKENLSYDLVPLKNGGVGIKVMYMGEEHLFSVEQITAM
LLTKLKETAENSLKKPVTDCVISVPSFFTDAERRSVLDAAQIVGLNCLRLMNDMTAVALN
YGIYKQDLPSLDEKPRIVVFVDMGHSAFQVSACAFNKGKLKVLGTAFDPFLGGKNFDEKL
VEHFCAEFKTKYKLDAKSKIRALLRLYQECEKLKKLMSSNSTDLPLNIECFMNDKDVSGK
MNRSQFEELCAELLQKIEVPLYSLLEQTHLKVEDVSAVEIVGGATRIPAVKERIAKFFGK
DISTTLNADEAVARGCALQCAILSPAFKVREFSVTDAVPFPISLIWNHDSEDTEGVHEVF
SRNHAAPFSKVLTFLRRGPFELEAFYSDPQGVPYPEAKIGRFVVQNVSAQKDGEKSRVKV
KVRVNTHGIFTISTASMVEKVPTEENEMSSEADMECLNQRPPENPDTDKNVQQDNSEAGT
QPQVQTDAQQTSQSPPSPELTSEENKIPDADKANEKKVDQPPEAKKPKIKVVNVELPIEA
NLVWQLGKDLLNMYIETEGKMIMQDKLEKERNDAKNAVEEYVYEFRDKLCGPYEKFICEQ
DHQNFLRLLTETEDWLYEEGEDQAKQAYVDKLEELMKIGTPVKVRFQEAEERPKMFEELG
QRLQHYAKIAADFRNKDEKYNHIDESEMKKVEKSVNEVMEWMNNVMNAQAKKSLDQDPVV
RAQEIKTKIKELNNTCEPVVTQPKPKIESPKLERTPNGPNIDKKEEDLEDKNNFGAEPPH
QNGECYPNEKNSVNMDLD

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Family Heat shock protein 70 family
Function
Acts as a nucleotide-exchange factor (NEF) for chaperone proteins HSPA1A and HSPA1B, promoting the release of ADP from HSPA1A/B thereby triggering client/substrate protein release. Prevents the aggregation of denatured proteins in cells under severe stress, on which the ATP levels decrease markedly. Inhibits HSPA8/HSC70 ATPase and chaperone activities (By similarity).

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HGNC ID
HGNC:16969
KEGG ID hsa:10808
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
HSPH1 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
Cystine/glutamate transporter (SLC7A11) [Driver; Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 GES-1 cells Normal Homo sapiens CVCL_EQ22
SGC-7901 cells Gastric carcinoma Homo sapiens CVCL_0520
HGC-27 cells Gastric carcinoma Homo sapiens CVCL_1279
AGS cells Gastric adenocarcinoma Homo sapiens CVCL_0139
MGC-803 cells Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
MKN45 cells Gastric adenocarcinoma Homo sapiens CVCL_0434
In Vivo Model
Four-week-old female BALB/c nude mice were purchased from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). For subsequent studies, the nude mice were randomly divided into four groups as follows: sh-Ctrl, sh-ATF2, sh-Ctrl + sorafenib and sh-ATF2 + sorafenib. Approximately 5 x 106 ATF2 knockdown or control MGC803 cells were subcutaneously injected into the axilla of nude mice. Beginning on Day 8, mice in the sorafenib treatment group received 10 mg/kg sorafenib by intraperitoneal injection every 2 days for 3 weeks.

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Response regulation Using ChIP-Seq and RNA-Seq, HSPH1 as a target of ATF2 and further validated it by ChIPqPCR analysis. HSPH1 can interact with SLC7A11 (cystine/glutamate transporter) and increase its protein stability. Importantly, knockdown of HSPH1 partly reversed the effects caused by ATF2 overexpression on sorafenib-induced ferroptosis in gastric cancer cells.
Gastric cancer [ICD-11: 2B72]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Heat shock protein 105 kDa (HSPH1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 GES-1 cells Normal Homo sapiens CVCL_EQ22
SGC-7901 cells Gastric carcinoma Homo sapiens CVCL_0520
HGC-27 cells Gastric carcinoma Homo sapiens CVCL_1279
AGS cells Gastric adenocarcinoma Homo sapiens CVCL_0139
MGC-803 cells Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
MKN45 cells Gastric adenocarcinoma Homo sapiens CVCL_0434
In Vivo Model
Four-week-old female BALB/c nude mice were purchased from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). For subsequent studies, the nude mice were randomly divided into four groups as follows: sh-Ctrl, sh-ATF2, sh-Ctrl + sorafenib and sh-ATF2 + sorafenib. Approximately 5 x 106 ATF2 knockdown or control MGC803 cells were subcutaneously injected into the axilla of nude mice. Beginning on Day 8, mice in the sorafenib treatment group received 10 mg/kg sorafenib by intraperitoneal injection every 2 days for 3 weeks.

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Response regulation Using ChIP-Seq and RNA-Seq, HSPH1 as a target of ATF2 and further validated it by ChIPqPCR analysis. HSPH1 can interact with SLC7A11 (cystine/glutamate transporter) and increase its protein stability. Importantly, knockdown of HSPH1 partly reversed the effects caused by ATF2 overexpression on sorafenib-induced ferroptosis in gastric cancer cells.
References
Ref 1 Increased ATF2 expression predicts poor prognosis and inhibits sorafenib-induced ferroptosis in gastric cancer. Redox Biol. 2023 Feb;59:102564. doi: 10.1016/j.redox.2022.102564. Epub 2022 Dec 2.