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Literature summary for 2.7.11.25 extracted from

  • Kim, S.; Ezhilarasan, R.; Phillips, E.; Gallego-Perez, D.; Sparks, A.; Taylor, D.; Ladner, K.; Furuta, T.; Sabit, H.; Chhipa, R.; Cho, J.; Mohyeldin, A.; Beck, S.; Kurozumi, K.; Kuroiwa, T.; Iwata, R.; Asai, A.; Kim, J.; Sulman, E.; Cheng, S.; Lee, L.
    Serine/threonine kinase MLK4 determines mesenchymal identity in glioma stem cells in an NF-kappaB-dependent manner (2016), Cancer Cell, 29, 201-213 .
    View publication on PubMedView publication on EuropePMC
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Protein Variants

Protein Variants Comment Organism
additional information MLK4 silencing with the short hairpin RNA (shRNA) technique Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + IKKalpha Homo sapiens
-
 ADP + phospho-IKKalpha
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q5TCX8
-
-

Source Tissue

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 and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + IKKalpha
-
 Homo sapiens ADP + phospho-IKKalpha
-
 ?

Synonyms

Synonyms Comment Organism
mixed lineage kinase 4
-
 Homo sapiens
MLK4
-
 Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Homo sapiens

Expression

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

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