Protein Variants | Comment | Organism |
---|---|---|
additional information | MLK4 silencing with the short hairpin RNA (shRNA) technique | Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + IKKalpha | Homo sapiens | - |
ADP + phospho-IKKalpha | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q5TCX8 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
astrocyte | - |
Homo sapiens | - |
glioblastoma cell | - |
Homo sapiens | - |
mesenchyme | - |
Homo sapiens | - |
additional information | mixed lineage kinase 4 (MLK4) is overexpressed in mesenchymal but not proneural glioma stem cells, GSCs | Homo sapiens | - |
proneural glioma stem cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + IKKalpha | - |
Homo sapiens | ADP + phospho-IKKalpha | - |
? |
Synonyms | Comment | Organism |
---|---|---|
mixed lineage kinase 4 | - |
Homo sapiens |
MLK4 | - |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Homo sapiens |
Organism | Comment | Expression |
---|---|---|
Homo sapiens | the MLK4 promoter is hypermethylated in proneural tumors with isocitrate dehydrogenase 1 (IDH1) mutation, suggesting that epigenetic silencing is one mechanism by which MLK4 is expressed at lower levels in proneural gliobalstomas | down |
Homo sapiens | mixed lineage kinase 4 (MLK4) is overexpressed in mesenchymal but not proneural glioma stem cells. gene MLK4 is significantly upregulated in mesenchymal glioma spheres by 4fold or more compared with proneural spheres and/or somatic cell types including normal neural progenitors and astrocytes. MLK4 expression is enriched in the stemness-associated ALDEFLUOR-positive subpopulations in MES 83 glioma spheres | up |
General Information | Comment | Organism |
---|---|---|
malfunction | silencing MLK4 suppresses self-renewal, motility, tumorigenesis, and radioresistance of mesenchymal glioma stem cells via a loss of the mesenchymal signature. Silencing MLK4 inhibits de novo and acquired (radiation-induced) mesenchymal glioma stem cells both in vitro and in vivo. Silencing MLK4 attenuates mesenchymal identity in glioma stem cells. Depletion of MLK4 attenuates a set of mesenchymal glioma stem cell phenotypes | Homo sapiens |
physiological function | MLK4 activates NF-kB signaling by direct phosphorylation of IKKalpha. MLK4 binds and phosphorylates the NF-kappaB regulator IKKa, leading to activation of NF-kappaB signaling in glioma stem cells. MLK4 expression is inversely correlated with patient prognosis in mesenchymal gliomas, but not proneural high-grade glioblastomas. MLK4 is an upstream regulator of NF-kappaB signaling and a potential molecular target for the mesenchymal subtype of glioblastomas. IKKalpha is a direct molecular target of MLK4 that drives the NF-kappaB pathway activation, thereby promoting mesenchymal transdifferentiation of glioma stem cells. MLK4 promotes radioresistance in glioblastoma. MLK4 is the only gene that is required for survival of mesenchymal, but not proneural, glioma spheres | Homo sapiens |