Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10336)
Regulator Name Nonsense-mediated mRNA decay factor SMG9 (SMG9)
Gene Name SMG9
Gene ID 56006
Regulator Type Protein coding
Uniprot ID Q9H0W8
Sequence
MSESGHSQPGLYGIERRRRWKEPGSGGPQNLSGPGGRERDYIAPWERERRDASEETSTSV
MQKTPIILSKPPAERSKQPPPPTAPAAPPAPAPLEKPIVLMKPREEGKGPVAVTGASTPE
GTAPPPPAAPAPPKGEKEGQRPTQPVYQIQNRGMGTAAPAAMDPVVGQAKLLPPERMKHS
IKLVDDQMNWCDSAIEYLLDQTDVLVVGVLGLQGTGKSMVMSLLSANTPEEDQRTYVFRA
QSAEMKERGGNQTSGIDFFITQERIVFLDTQPILSPSILDHLINNDRKLPPEYNLPHTYV
EMQSLQIAAFLFTVCHVVIVVQDWFTDLSLYRFLQTAEMVKPSTPSPSHESSSSSGSDEG
TEYYPHLVFLQNKARREDFCPRKLRQMHLMIDQLMAHSHLRYKGTLSMLQCNVFPGLPPD
FLDSEVNLFLVPFMDSEAESENPPRAGPGSSPLFSLLPGYRGHPSFQSLVSKLRSQVMSM
ARPQLSHTILTEKNWFHYAARIWDGVRKSSALAEYSRLLA

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Family SMG9 family
Function
Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Is recruited by release factors to stalled ribosomes together with SMG1 and SMG8 (forming the SMG1C protein kinase complex) and, in the SMG1C complex, is required for the efficient association between SMG1 and SMG8. Plays a role in brain, heart, and eye development.

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HGNC ID
HGNC:25763
KEGG ID hsa:56006
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
SMG9 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
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 [1]
Target for Ferroptosis Suppressor
Responsed Disease Pancreatic cancer ICD-11: 2C10
 Disease Info 
Responsed Drug RSL3 Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
In Vivo Model
To generate murine subcutaneous tumors, 5 x 106 PANC1 cells in 100 ul PBS were injected subcutaneously to the right of the dorsal midline in 6- to 8-week-oldathymic nude mice(n = 5 mice/group). After the tumor reached 60-80 mm3 on day 7, the mice were randomly grouped and then given intratumoral treatment with RSL3 (50 mg/kg, once every other day) at day 7 for 2 weeks.

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Response regulation SMG9, a component of the NMD machinery, is a selective driver for ferroptosis in pancreatic cancer cells. SMG9 is a direct binding protein of GPX4 to promote the degradation of GPX4 in response to RSL3 (a GPX4 inhibitor), but not erastin (a SLC7A11 inhibitor).
Pancreatic cancer [ICD-11: 2C10]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Nonsense-mediated mRNA decay factor SMG9 (SMG9) Protein coding
 Regulator Info 
Responsed Drug RSL3 Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
In Vivo Model
To generate murine subcutaneous tumors, 5 x 106 PANC1 cells in 100 ul PBS were injected subcutaneously to the right of the dorsal midline in 6- to 8-week-oldathymic nude mice(n = 5 mice/group). After the tumor reached 60-80 mm3 on day 7, the mice were randomly grouped and then given intratumoral treatment with RSL3 (50 mg/kg, once every other day) at day 7 for 2 weeks.

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Response regulation SMG9, a component of the NMD machinery, is a selective driver for ferroptosis in pancreatic cancer cells. SMG9 is a direct binding protein of GPX4 to promote the degradation of GPX4 in response to RSL3 (a GPX4 inhibitor), but not erastin (a SLC7A11 inhibitor).
RSL3 [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Phospholipid hydroperoxide glutathione peroxidase (GPX4) Suppressor
 Target Info 
Responsed Disease Pancreatic cancer ICD-11: 2C10
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
In Vivo Model
To generate murine subcutaneous tumors, 5 x 106 PANC1 cells in 100 ul PBS were injected subcutaneously to the right of the dorsal midline in 6- to 8-week-oldathymic nude mice(n = 5 mice/group). After the tumor reached 60-80 mm3 on day 7, the mice were randomly grouped and then given intratumoral treatment with RSL3 (50 mg/kg, once every other day) at day 7 for 2 weeks.

    Click to Show/Hide
Response regulation SMG9, a component of the NMD machinery, is a selective driver for ferroptosis in pancreatic cancer cells. SMG9 is a direct binding protein of GPX4 to promote the degradation of GPX4 in response to RSL3 (a GPX4 inhibitor), but not erastin (a SLC7A11 inhibitor).
References
Ref 1 SMG9 drives ferroptosis by directly inhibiting GPX4 degradation. Biochem Biophys Res Commun. 2021 Aug 27;567:92-98. doi: 10.1016/j.bbrc.2021.06.038. Epub 2021 Jun 16.