Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10405)
Regulator Name DNA damage-inducible transcript 4 protein (DDIT4)
Synonyms
REDD1; RTP801; HIF-1 responsive protein RTP801; Protein regulated in development and DNA damage response 1 (REDD-1)
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Gene Name DDIT4
Gene ID 54541
Regulator Type Protein coding
Uniprot ID Q9NX09
Sequence
MPSLWDRFSSSSTSSSPSSLPRTPTPDRPPRSAWGSATREEGFDRSTSLESSDCESLDSS
NSGFGPEEDTAYLDGVSLPDFELLSDPEDEHLCANLMQLLQESLAQARLGSRRPARLLMP
SQLVSQVGKELLRLAYSEPCGLRGALLDVCVEQGKSCHSVGQLALDPSLVPTFQLTLVLR
LDSRLWPKIQGLFSSANSPFLPGFSQSLTLSTGFRVIKKKLYSSEQLLIEEC

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Family DDIT4 family
Function
Regulates cell growth, proliferation and survival via inhibition of the activity of the mammalian target of rapamycin complex 1 (mTORC1). Inhibition of mTORC1 is mediated by a pathway that involves DDIT4/REDD1, AKT1, the TSC1-TSC2 complex and the GTPase RHEB. Plays an important role in responses to cellular energy levels and cellular stress, including responses to hypoxia and DNA damage. Regulates p53/TP53-mediated apoptosis in response to DNA damage via its effect on mTORC1 activity. Its role in the response to hypoxia depends on the cell type; it mediates mTORC1 inhibition in fibroblasts and thymocytes, but not in hepatocytes. Required for mTORC1-mediated defense against viral protein synthesis and virus replication. Inhibits neuronal differentiation and neurite outgrowth mediated by NGF via its effect on mTORC1 activity. Required for normal neuron migration during embryonic brain development. Plays a role in neuronal cell death.

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HGNC ID
HGNC:24944
KEGG ID hsa:54541
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
DDIT4 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 Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 PC-9 cells Lung adenocarcinoma Homo sapiens CVCL_B260
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
In Vivo Model
The animal studies were approved by the Institutional Animal Care and Use Committee (IACUC) of Second Xiangya Hospital following the Guidelines of the Care and Use of Laboratory Animals issued by the Chinese Council on Animal Research. Briefly, female BALB/c nude mice at six weeks were obtained from Hunan SJA Laboratory Animal Co. Ltd. (Hunan, China) and kept in a specific pathogen-free environment. The mice were injected subcutaneously with 2 x 106 indicated cells into the left or right flank for 21 days (PC9) or 28 days (A549) post-implantation. At the end of the experiment, the tumours were dissected and weighed.

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Response regulation LINC00551 acts as a competing endogenous RNA (ceRNA) and binds with miR-4328 which up-regulates the target DNA damage-inducible transcript 4 (DDIT4). DDIT4 inhibits the activity of mTOR, promotes lung adenocarcinoma (LUAD) autophagy, and then promotes the ferroptosis of LUAD cells in an autophagy-dependent manner.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator DNA damage-inducible transcript 4 protein (DDIT4) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 PC-9 cells Lung adenocarcinoma Homo sapiens CVCL_B260
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
In Vivo Model
The animal studies were approved by the Institutional Animal Care and Use Committee (IACUC) of Second Xiangya Hospital following the Guidelines of the Care and Use of Laboratory Animals issued by the Chinese Council on Animal Research. Briefly, female BALB/c nude mice at six weeks were obtained from Hunan SJA Laboratory Animal Co. Ltd. (Hunan, China) and kept in a specific pathogen-free environment. The mice were injected subcutaneously with 2 x 106 indicated cells into the left or right flank for 21 days (PC9) or 28 days (A549) post-implantation. At the end of the experiment, the tumours were dissected and weighed.

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Response regulation LINC00551 acts as a competing endogenous RNA (ceRNA) and binds with miR-4328 which up-regulates the target DNA damage-inducible transcript 4 (DDIT4). DDIT4 inhibits the activity of mTOR, promotes lung adenocarcinoma (LUAD) autophagy, and then promotes the ferroptosis of LUAD cells in an autophagy-dependent manner.
References
Ref 1 Overexpression of LINC00551 promotes autophagy-dependent ferroptosis of lung adenocarcinoma via upregulating DDIT4 by sponging miR-4328. PeerJ. 2022 Oct 12;10:e14180. doi: 10.7717/peerj.14180. eCollection 2022.