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:22824791

From GONUTS
Jump to: navigation, search
Citation

Skalka, N, Caspi, M, Caspi, E, Loh, YP and Rosin-Arbesfeld, R (2012) Carboxypeptidase E: a negative regulator of the canonical Wnt signaling pathway. ' '

Abstract

Aberrant activation of the canonical Wnt signal transduction pathway is involved in many diseases including cancer and is especially implicated in the development and progression of colorectal cancer. The key effector protein of the canonical Wnt pathway is β-catenin, which functions with T-cell factor/lymphoid enhancer factor to activate expression of Wnt target genes. In this study, we used a new functional screen based on cell survival in the presence of cDNAs encoding proteins that activate the Wnt pathway thus identifying novel Wnt signaling components. Here we identify carboxypeptidase E (|CPE) and its splice variant, ΔN-CPE, as novel regulators of the Wnt pathway. We show that whereas ΔN-CPE activates the Wnt signal, the full-length CPE (F-CPE) protein is an inhibitor of Wnt/β-catenin signaling. F-CPE forms a complex with the Wnt3a ligand and the Frizzled receptor. Moreover, F-CPE disrupts disheveled-induced signalosomes that are important for transducing the Wnt signal and reduces β-catenin protein levels and activity. Taken together, our data indicate that F-CPE and ΔN-CPE regulate the canonical Wnt signaling pathway negatively and positively, respectively, and demonstrate that this screening approach can be a rapid means for isolation of novel Wnt signaling components.Oncogene advance online publication, 23 July 2012; doi:10.1038/onc.2012.308.

Links

PubMed Online version:10.1038/onc.2012.308

Keywords


Significance

Annotations

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

HUMAN:CBPE

GO:0016055 : Wnt receptor signaling pathway

ECO:0000314:

P

Figure 1.

complete
CACAO 5203

HUMAN:CBPE

GO:0030877: beta-catenin destruction complex

ECO:0000314:

C

Figure 2.

complete
CACAO 5205

HUMAN:CBPE

GO:0004175: endopeptidase activity

ECO:0000314:

F

Figure 3.

complete
CACAO 5207

HUMAN:CBPE

involved_in

GO:0016055: Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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