GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:22304967

From GONUTS
Jump to: navigation, search
Citation

Hanson, AJ, Wallace, HA, Freeman, TJ, Beauchamp, RD, Lee, LA and Lee, E (2012) XIAP monoubiquitylates Groucho/TLE to promote canonical Wnt signaling. Mol. Cell 45:619-28

Abstract

A key event in Wnt signaling is conversion of TCF/Lef from a transcriptional repressor to an activator, yet how this switch occurs is not well understood. Here, we report an unanticipated role for X-linked inhibitor of apoptosis (XIAP) in regulating this critical Wnt signaling event that is independent of its antiapoptotic function. We identified DIAP1 as a positive regulator of Wingless signaling in a Drosophila S2 cell-based RNAi screen. XIAP, its vertebrate homolog, is similarly required for Wnt signaling in cultured mammalian cells and in Xenopus embryos, indicating evolutionary conservation of function. Upon Wnt pathway activation, XIAP is recruited to TCF/Lef where it monoubiquitylates Groucho (Gro)/TLE. This modification decreases affinity of Gro/TLE for TCF/Lef. Our data reveal a transcriptional switch involving XIAP-mediated ubiquitylation of Gro/TLE that facilitates its removal from TCF/Lef, thus allowing β-catenin-TCF/Lef complex assembly and initiation of a Wnt-specific transcriptional program.

Links

PubMed PMC3299836 Online version:10.1016/j.molcel.2011.12.032

Keywords

Animals; Co-Repressor Proteins/metabolism; Drosophila/genetics; Drosophila/metabolism; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila Proteins/physiology; Embryo, Nonmammalian/metabolism; HEK293 Cells; Humans; Inhibitor of Apoptosis Proteins/genetics; Inhibitor of Apoptosis Proteins/metabolism; Inhibitor of Apoptosis Proteins/physiology; Models, Genetic; RNA Interference; Ubiquitination; Wnt Proteins/metabolism; Wnt Signaling Pathway; Wnt1 Protein/metabolism; X-Linked Inhibitor of Apoptosis Protein/genetics; X-Linked Inhibitor of Apoptosis Protein/metabolism; X-Linked Inhibitor of Apoptosis Protein/physiology; Xenopus; Xenopus Proteins/metabolism

Significance

Annotations

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

XENLA:XIAP

involved_in

GO:0090263: positive regulation of canonical Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:XIAP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q04726

F

Seeded From UniProt

complete

HUMAN:XIAP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9NQB0

F

Seeded From UniProt

complete

HUMAN:XIAP

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:XIAP

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:XIAP

enables

GO:0004842: ubiquitin-protein transferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:XIAP

involved_in

GO:0090263: positive regulation of canonical Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:XIAP

enables

GO:0061630: ubiquitin protein ligase activity

ECO:0000269: experimental evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:TLE3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P98170

F

Seeded From UniProt

complete

HUMAN:TLE3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9NQB0

F

Seeded From UniProt

complete

DROME:DIAP1

enables

GO:0004842: ubiquitin-protein transferase activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

DROME:DIAP1

involved_in

GO:0090263: positive regulation of canonical Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TF7L2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q04726

F

Seeded From UniProt

complete

HUMAN:TF7L2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P98170

F

Seeded From UniProt

complete

DROME:IAP1

enables

GO:0004842: ubiquitin-protein transferase activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

DROME:IAP1

involved_in

GO:0090263: positive regulation of canonical Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.