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PMID:10830967

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Citation

Petcherski, AG and Kimble, J (2000) LAG-3 is a putative transcriptional activator in the C. elegans Notch pathway. Nature 405:364-8

Abstract

Notch signalling controls growth, differentiation and patterning during normal animal development; in humans, aberrant Notch signalling has been implicated in cancer and stroke. The mechanism of Notch signalling is thought to require cleavage of the receptor in response to ligand binding, movement of the receptor's intracellular domain to the nucleus, and binding of that intracellular domain to a CSL (for CBF1, Suppressor of Hairless, LAG-1) protein. Here we identify LAG-3, a glutamine-rich protein that forms a ternary complex together with the LAG-1 DNA-binding protein and the receptor's intracellular domain. Receptors with mutant ankyrin repeats that abrogate signal transduction are incapable of complex formation both in yeast and in vitro. Using RNA interference, we find that LAG-3 activity is crucial in Caenorhabditis elegans for both GLP-1 and LIN-12 signalling. LAG-3 is a potent transcriptional activator in yeast, and a Myc-tagged LAG-3 is predominantly nuclear in C. elegans. We propose that GLP-1 and LIN-12 promote signalling by recruiting LAG-3 to target promoters, where it functions as a transcriptional activator.

Links

PubMed Online version:10.1038/35012645

Keywords

Amino Acid Sequence; Animals; Ankyrin Repeat; Caenorhabditis elegans/genetics; Caenorhabditis elegans Proteins; DNA, Helminth/metabolism; DNA-Binding Proteins/analysis; DNA-Binding Proteins/genetics; DNA-Binding Proteins/physiology; Escherichia coli; Glutamine/metabolism; Helminth Proteins/analysis; Helminth Proteins/genetics; Helminth Proteins/isolation & purification; Helminth Proteins/metabolism; Helminth Proteins/physiology; Membrane Glycoproteins/genetics; Membrane Glycoproteins/metabolism; Membrane Proteins/genetics; Membrane Proteins/metabolism; Molecular Sequence Data; Mutagenesis; Promoter Regions, Genetic; RNA, Helminth/metabolism; Receptors, Notch; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; Signal Transduction; Trans-Activators/genetics; Trans-Activators/isolation & purification; Trans-Activators/physiology; Two-Hybrid System Techniques; Yeasts/genetics

Significance

Annotations

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

CAEEL:GLP1

part_of

GO:0090575: RNA polymerase II transcription regulator complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:LIN12

part_of

GO:0090575: RNA polymerase II transcription regulator complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:LAG3

part_of

GO:0090575: RNA polymerase II transcription regulator complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:LAG3

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:LAG3

involved_in

GO:0007219: Notch signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:LAG3

involved_in

GO:0007219: Notch signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:LAG3

enables

GO:0003713: transcription coactivator activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(WB:WBGene00002245)

Seeded From UniProt

complete

CAEEL:LAG3

involved_in

GO:2000648: positive regulation of stem cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:LAG3

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:LAG1

part_of

GO:0090575: RNA polymerase II transcription regulator complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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