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PMID:15062575

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Citation

Eckey, M, Tenbaum, SP, Muñoz, A and Baniahmad, A (2003) Mixed lineage kinase 2 enhances trans-repression of Alien and nuclear receptors. Mol. Cell. Endocrinol. 213:71-8

Abstract

Alien was previously identified as a corepressor for the thyroid hormone receptor (TR) and DAX-1 which belong both to the superfamily of nuclear receptors. Here, we isolated the mixed lineage kinase 2 (MLK2) as an interacting partner for the corepressor Alien using a yeast two hybrid screen. MLK2 is an upstream activator of JNKs and activation of MLK2-mediated signaling cascades play roles in neurodegenerative and apoptotic mechanisms in the central nervous system. MLK2 has been shown to be localized both in the cytoplasm and cell nucleus. We confirmed the Alien-MLK2 interaction using GST pull-down experiments and also show that MLK2 is able to phosphorylate Alien in immune-kinase assays. Functional analyses revealed that Alien, DAX-1 and thyroid hormone receptor mediated transcriptional silencing is strongly enhanced in the presence of active MLK2. Since MAP kinase signaling pathways are important mediators of cellular responses to a wide variety of stimuli, our data suggest that signaling pathways not only regulate transactivation but also enhancement of transcriptional silencing. This novel cross-talk may represent a link between MLK2-mediated signaling and transcriptional repression of target genes during neuronal differentiation processes.

Links

PubMed Online version:10.1016/j.mce.2003.10.035

Keywords

DAX-1 Orphan Nuclear Receptor; DNA-Binding Proteins/physiology; Gene Silencing; MAP Kinase Kinase Kinases/metabolism; MAP Kinase Kinase Kinases/physiology; Protein Binding; Receptor Cross-Talk; Receptors, Cytoplasmic and Nuclear/metabolism; Receptors, Cytoplasmic and Nuclear/physiology; Receptors, Retinoic Acid/physiology; Receptors, Thyroid Hormone/physiology; Repressor Proteins/metabolism; Repressor Proteins/physiology; Signal Transduction

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:THB

acts_upstream_of_or_within

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CSN2

enables

GO:0003714: transcription corepressor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:CSN2

acts_upstream_of_or_within

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:THA

acts_upstream_of_or_within

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NR0B1

acts_upstream_of_or_within

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:M3K10

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P61201

F

Seeded From UniProt

complete

MOUSE:M3K10

acts_upstream_of_or_within

GO:0006468: protein phosphorylation

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P61201

P

Seeded From UniProt

complete

MOUSE:M3K10

enables

GO:0004672: protein kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:M3K10

enables

GO:0003714: transcription corepressor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:M3K10

acts_upstream_of_or_within

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

See also

References

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