Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10227)
Regulator Name Mitogen-activated protein kinase kinase kinase 11 (MAP3K11)
Synonyms
Mixed lineage kinase 3; Src-homology 3 domain-containing proline-rich kinase
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Gene Name MAP3K11
Gene ID 4296
Regulator Type Protein coding
Uniprot ID Q16584
Sequence
MEPLKSLFLKSPLGSWNGSGSGGGGGGGGGRPEGSPKAAGYANPVWTALFDYEPSGQDEL
ALRKGDRVEVLSRDAAISGDEGWWAGQVGGQVGIFPSNYVSRGGGPPPCEVASFQELRLE
EVIGIGGFGKVYRGSWRGELVAVKAARQDPDEDISVTAESVRQEARLFAMLAHPNIIALK
AVCLEEPNLCLVMEYAAGGPLSRALAGRRVPPHVLVNWAVQIARGMHYLHCEALVPVIHR
DLKSNNILLLQPIESDDMEHKTLKITDFGLAREWHKTTQMSAAGTYAWMAPEVIKASTFS
KGSDVWSFGVLLWELLTGEVPYRGIDCLAVAYGVAVNKLTLPIPSTCPEPFAQLMADCWA
QDPHRRPDFASILQQLEALEAQVLREMPRDSFHSMQEGWKREIQGLFDELRAKEKELLSR
EEELTRAAREQRSQAEQLRRREHLLAQWELEVFERELTLLLQQVDRERPHVRRRRGTFKR
SKLRARDGGERISMPLDFKHRITVQASPGLDRRRNVFEVGPGDSPTFPRFRAIQLEPAEP
GQAWGRQSPRRLEDSSNGERRACWAWGPSSPKPGEAQNGRRRSRMDEATWYLDSDDSSPL
GSPSTPPALNGNPPRPSLEPEEPKRPVPAERGSSSGTPKLIQRALLRGTALLASLGLGRD
LQPPGGPGRERGESPTTPPTPTPAPCPTEPPPSPLICFSLKTPDSPPTPAPLLLDLGIPV
GQRSAKSPRREEEPRGGTVSPPPGTSRSAPGTPGTPRSPPLGLISRPRPSPLRSRIDPWS
FVSAGPRPSPLPSPQPAPRRAPWTLFPDSDPFWDSPPANPFQGGPQDCRAQTKDMGAQAP
WVPEAGP

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Family STE Ser/Thr protein kinase family
Function
Activates the JUN N-terminal pathway. Required for serum- stimulated cell proliferation and for mitogen and cytokine activation of MAPK14 (p38), MAPK3 (ERK) and MAPK8 (JNK1) through phosphorylation and activation of MAP2K4/MKK4 and MAP2K7/MKK7. Plays a role in mitogen- stimulated phosphorylation and activation of BRAF, but does not phosphorylate BRAF directly. Influences microtubule organization during the cell cycle.

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HGNC ID
HGNC:6850
KEGG ID hsa:4296
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
MAP3K11 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
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Unspecific Target [Unspecific Target]
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Lung injury ICD-11: NB32
 Disease Info 
Responsed Drug Lipopolysaccharide Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MLE-12 cells Normal Mus musculus CVCL_3751
Response regulation Silence of MLK3 (MAP3K11) alleviated Lipopolysaccharide (LPS)-induced lung epithelial cell injury by inhibiting p53-mediated ferroptosis, suggesting that MLK3 may be a potential target to prevent acute lung injury.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [2]
Responsed Disease Chronic heart failure ICD-11: BD1Z
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Necroptosis hsa04217
NF-kappa B signaling pathway hsa04064
Cell Process Cell ferroptosis
Cell pyroptosis
In Vitro Model
 rHTs (Rat hippocampal tissues)
In Vivo Model
Male wild-type (WT) C57BL/6J mice aged 8 weeks were obtained from the Experimental Animal Center, Guangzhou University of Chinese Medicine. Sham and TAC mice received corresponding isotype i.p. injections. TAC + AAVMLK3- mice were generated by intravenous (i.v.) injection of adeno-associated viral vector-MLK3 vector (AAVMLK3-) (GenePharma, Shanghai, China) 14 and 21 days before TAC surgery. Sham + AAVNC and TAC + AAVNC mice received AAVNC i.v. injections. TAC + antagomir and TAC + agomir were generated by i.v. injection of antagomir and agomir (30 pmol/g) 14 and 21 days before TAC surgery, respectively.

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Response regulation MLK3 (MAP3K11) mainly regulates the JNK/p53 signaling pathway-mediated oxidative stress and that ferroptosis causes myocardial fibrosis in the advanced stages of chronic heart failure (CHF). Promoting the expression of miR-351 can inhibit the expression of MLK3, and significantly improve cardiac function in mice subjected to TAC.
Lung injury [ICD-11: NB32]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Mitogen-activated protein kinase kinase kinase 11 (MAP3K11) Protein coding
 Regulator Info 
Responsed Drug Lipopolysaccharide Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MLE-12 cells Normal Mus musculus CVCL_3751
Response regulation Silence of MLK3 (MAP3K11) alleviated Lipopolysaccharide (LPS)-induced lung epithelial cell injury by inhibiting p53-mediated ferroptosis, suggesting that MLK3 may be a potential target to prevent acute lung injury.
Chronic heart failure [ICD-11: BD1Z]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Mitogen-activated protein kinase kinase kinase 11 (MAP3K11) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Necroptosis hsa04217
NF-kappa B signaling pathway hsa04064
Cell Process Cell ferroptosis
Cell pyroptosis
In Vitro Model
 rHTs (Rat hippocampal tissues)
In Vivo Model
Male wild-type (WT) C57BL/6J mice aged 8 weeks were obtained from the Experimental Animal Center, Guangzhou University of Chinese Medicine. Sham and TAC mice received corresponding isotype i.p. injections. TAC + AAVMLK3- mice were generated by intravenous (i.v.) injection of adeno-associated viral vector-MLK3 vector (AAVMLK3-) (GenePharma, Shanghai, China) 14 and 21 days before TAC surgery. Sham + AAVNC and TAC + AAVNC mice received AAVNC i.v. injections. TAC + antagomir and TAC + agomir were generated by i.v. injection of antagomir and agomir (30 pmol/g) 14 and 21 days before TAC surgery, respectively.

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Response regulation MLK3 (MAP3K11) mainly regulates the JNK/p53 signaling pathway-mediated oxidative stress and that ferroptosis causes myocardial fibrosis in the advanced stages of chronic heart failure (CHF). Promoting the expression of miR-351 can inhibit the expression of MLK3, and significantly improve cardiac function in mice subjected to TAC.
Lipopolysaccharide [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 Lung injury ICD-11: NB32
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MLE-12 cells Normal Mus musculus CVCL_3751
Response regulation Silence of MLK3 (MAP3K11) alleviated Lipopolysaccharide (LPS)-induced lung epithelial cell injury by inhibiting p53-mediated ferroptosis, suggesting that MLK3 may be a potential target to prevent acute lung injury.
References
Ref 1 Silence of MLK3 alleviates lipopolysaccharide-induced lung epithelial cell injury via inhibiting p53-mediated ferroptosis. J Mol Histol. 2022 Apr;53(2):503-510. doi: 10.1007/s10735-022-10064-y. Epub 2022 Mar 5.
Ref 2 Pyroptosis and ferroptosis induced by mixed lineage kinase 3 (MLK3) signaling in cardiomyocytes are essential for myocardial fibrosis in response to pressure overload. Cell Death Dis. 2020 Jul 24;11(7):574. doi: 10.1038/s41419-020-02777-3.