Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10030)
Regulator Name Ragulator complex protein LAMTOR5 (LAMTOR5)
Synonyms
Hepatitis B virus X-interacting protein; Late endosomal/lysosomal adaptor and MAPK and MTOR activator 5
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Gene Name LAMTOR5
Gene ID 10542
Regulator Type Protein coding
Uniprot ID O43504
Sequence
MEATLEQHLEDTMKNPSIVGVLCTDSQGLNLGCRGTLSDEHAGVISVLAQQAAKLTSDPT
DIPVVCLESDNGNIMIQKHDGITVAVHKMAS

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Family LAMTOR5 family
Function
As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V- ATPase, the Ragulator functions as a guanine nucleotide exchange factor activating the small GTPases Rag. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. When complexed to BIRC5, interferes with apoptosome assembly, preventing recruitment of pro-caspase-9 to oligomerized APAF1, thereby selectively suppressing apoptosis initiated via the mitochondrial/cytochrome c pathway. Down-regulates hepatitis B virus (HBV) replication.

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HGNC ID
HGNC:17955
KEGG ID hsa:10542
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
LAMTOR5 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).
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Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Responsed Drug Sorafenib Investigative
 Drug Info 
Pathway Response Glutathione metabolism hsa00480
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
SMMC-7721 cells Endocervical adenocarcinoma Homo sapiens CVCL_0534
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
BEL-7402 cells Endocervical adenocarcinoma Homo sapiens CVCL_5492
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
Six-week-old male BALB/c athymic nude mice were purchased from the Experimental Animal Center of Peking (Beijing, China). Stable cells (5 x 106) were seeded into the right flanks of the mice. After the xenografts had grown to 200 mm3, saline as a vehicle or sorafenib (30 mg/kg) was administered by gavage every day, and the mice were euthanized by the cervical dislocation method five weeks later. Before sacrifice, the tumor sizes and body weights were measured twice per week. The tumor volume (V) was calculated as follows: (L x W2)/2 (length, L, and width, W). The xenografts were excised and further assessed.

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Response regulation Sorafenib decreased HBXIP expression, and overexpression of HBXIP blocked sorafenib-induced hepatocellular carcinoma cell death. Regarding the molecular mechanism, HBXIP transcriptionally induced the expression of stearoyl-CoA desaturase (SCD) via coactivating the transcriptional factor ZNF263, resulting in the accumulation of free fatty acids and suppression of ferroptosis.
Hepatocellular carcinoma [ICD-11: 2C12]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Ragulator complex protein LAMTOR5 (LAMTOR5) Protein coding
 Regulator Info 
Responsed Drug Sorafenib Investigative
 Drug Info 
Pathway Response Glutathione metabolism hsa00480
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
SMMC-7721 cells Endocervical adenocarcinoma Homo sapiens CVCL_0534
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
BEL-7402 cells Endocervical adenocarcinoma Homo sapiens CVCL_5492
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
Six-week-old male BALB/c athymic nude mice were purchased from the Experimental Animal Center of Peking (Beijing, China). Stable cells (5 x 106) were seeded into the right flanks of the mice. After the xenografts had grown to 200 mm3, saline as a vehicle or sorafenib (30 mg/kg) was administered by gavage every day, and the mice were euthanized by the cervical dislocation method five weeks later. Before sacrifice, the tumor sizes and body weights were measured twice per week. The tumor volume (V) was calculated as follows: (L x W2)/2 (length, L, and width, W). The xenografts were excised and further assessed.

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Response regulation Sorafenib decreased HBXIP expression, and overexpression of HBXIP blocked sorafenib-induced hepatocellular carcinoma cell death. Regarding the molecular mechanism, HBXIP transcriptionally induced the expression of stearoyl-CoA desaturase (SCD) via coactivating the transcriptional factor ZNF263, resulting in the accumulation of free fatty acids and suppression of ferroptosis.
Sorafenib [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 Unspecific Target
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Pathway Response Glutathione metabolism hsa00480
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
SMMC-7721 cells Endocervical adenocarcinoma Homo sapiens CVCL_0534
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
BEL-7402 cells Endocervical adenocarcinoma Homo sapiens CVCL_5492
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
Six-week-old male BALB/c athymic nude mice were purchased from the Experimental Animal Center of Peking (Beijing, China). Stable cells (5 x 106) were seeded into the right flanks of the mice. After the xenografts had grown to 200 mm3, saline as a vehicle or sorafenib (30 mg/kg) was administered by gavage every day, and the mice were euthanized by the cervical dislocation method five weeks later. Before sacrifice, the tumor sizes and body weights were measured twice per week. The tumor volume (V) was calculated as follows: (L x W2)/2 (length, L, and width, W). The xenografts were excised and further assessed.

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Response regulation Sorafenib decreased HBXIP expression, and overexpression of HBXIP blocked sorafenib-induced hepatocellular carcinoma cell death. Regarding the molecular mechanism, HBXIP transcriptionally induced the expression of stearoyl-CoA desaturase (SCD) via coactivating the transcriptional factor ZNF263, resulting in the accumulation of free fatty acids and suppression of ferroptosis.
References
Ref 1 Sorafenib triggers ferroptosis via inhibition of HBXIP/SCD axis in hepatocellular carcinoma. Acta Pharmacol Sin. 2023 Mar;44(3):622-634. doi: 10.1038/s41401-022-00981-9. Epub 2022 Sep 15.