Search results for APC

Showing 25 results out of 319

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Protein (4 results from a total of 115)

APC

Identifier: R-HSA-2976015
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: APC: P25054

APC

Identifier: R-HSA-3361755
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: APC: P25054
Identifier: R-HSA-5251499
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: APC: P25054
Identifier: R-HSA-4791251
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: APC: P25054

Reaction (4 results from a total of 106)

Identifier: R-HSA-5246693
Species: Homo sapiens
Compartment: cytosol
In unstimulated cells, APC is K63 polyubiquitinated in a manner that depends on its association with AXIN. Although the precise timing of APC polyubiquitination is unclear, it is disrupted by abrogation of GSK3 kinase activity and in the presence of phosphodegron mutants of beta-catenin, suggesting that the formation of a functional destruction complex is required. Destruction complex formation is also dependent upon AXIN levels, which may be regulated at least in part by the balance of its ubiquitination and sumoylation (Kim et al, 2008).
Upon WNT3A stimulation, APC K63 polyubiquitination is lost coincident with disruption of the APC-AXIN interaction (Tran and Polakis, 2012). Interestingly, another study has shown that DVL is K63 polyubiquitinated upon WNT signaling (Tauriello et al, 2010), suggesting a possible model in which WNT signaling promotes a change in AXIN-K63 polyubiquitin binding partner to destabilize the destruction complex and promote pathway activation. Alternately, APC K63 polyubiquitination may protect beta-catenin from PP2A-mediated dephosphorylation and thus favour its degradation (Su et al, 2008).
Identifier: R-HSA-6781905
Species: Homo sapiens
Compartment: cytosol
ZRANB1 (Trabid) binds and cleaves K63-linked ubiquitin chains. It is required for efficient TCF-mediated transcription in cells with high Wnt pathway activity, including colorectal cancer cell lines. ZRANB1 can deubiquitinate the APC tumor suppressor protein, a negative regulator of Wnt-mediated transcription (Tran et al. 2008).
Identifier: R-HSA-202947
Species: Homo sapiens
Compartment: cytosol
Cleavage of APC by caspase 3 and release of the amino-terminal fragment (1-760) are required for the APC mediated acceleration of apoptosis-associated caspase activity (Qian et al., 2007).
Identifier: R-HSA-195275
Species: Homo sapiens
Compartment: cytosol
APC is phosphorylated on the 20 aa repeats by CK1 and potentially GSK-3. This significantly increases the binding affinity of the APC 20 aa repeats for beta-catenin, causing one of them to bind b-catenin in the same region as beta-catenin binds Axin, thus displacing beta-catenin from Axin ( Step 5 above) (Reviewed in Kimelman, 2006).

Pathway (4 results from a total of 49)

Identifier: R-HSA-4839744
Species: Homo sapiens
Compartment: cytosol
APC is a large and central component of the destruction complex, which limits signaling in the absence of WNT ligand by promoting the ubiquitin-mediated degradation of beta-catenin. APC interacts with numerous components of the destruction complex, including AXINs (AXIN1 and AXIN2), GSK3s (GSK3alpha and GSK3beta), CK1, PP2A and beta-catenin, and these interactions are critical for the phosphorylation and degradation of beta-catenin (reviewed in Saito-Diaz et al, 2013). APC is itself the target of phosphorylation and K63 ubiquitination in the absence of WNT signaling and these modifications are required for its interactions with other components of the destruction complex (Tran and Polakis, 2012; Ha et al, 2004; reviewed in Stamos and Weis, 2013).

More than 85% of sporadic and hereditary colorectal tumors carry loss-of-function mutations in APC. Most of the mutations are frameshifts and result in truncated proteins that lack the SAMP motifs and the 15 and 20 aa repeats that are implicated in binding AXIN and regulating beta-catenin binding and degradation (Miyoshi et al, 1992; Nagase and Nakamura, 1993; reviewed in Segditas and Tomlinson, 2006). Cancers expressing truncated APC have high levels of cytoplasmic beta-catenin and deregulated expression of WNT target genes (Korinek et al, 1997). Approximately 15% of the colorectal tumors with wild-type APC harbor phosphodegron mutations of beta-catenin; interestingly, mutations in APC and beta-catenin are mutually exclusive events. Similar to APC-mutant tumors, beta-catenin is stabilized in these tumors and constitutive WNT target activation is detected (Morin et al, 1997; reviewed in Polakis, 2000).

Identifier: R-HSA-5467333
Species: Homo sapiens
APC has been shown to be reversibly modified with K63-linked polyubiquitin chains. This modification is required for the assembly of the destruction complex and subsequent degradation of beta-catenin in the absence of WNT ligand. K63-polyubiquitination of APC is lacking in a number of colorectal cancer cell lines expressing truncated forms of APC, and these lines have aberrantly high beta-catenin levels and WNT pathway activation (Tran and Polakis, 2012).
Identifier: R-HSA-5467337
Species: Homo sapiens
Mutations in the APC tumor suppressor gene are common in colorectal and other cancers and cluster in the central mutation cluster region (MCR) of the gene (Miyoshi et al, 1992; Nagase and Nakamura, 1993; Dihlmann et al, 1999; reviewed in Bienz and Clevers, 2000). These mutations generally result in truncated proteins that destabilize the destruction complex and result in elevated WNT pathway activation (reviewed in Polakis, 2000).
Identifier: R-HSA-176412
Species: Homo sapiens
Compartment: nucleoplasm
Phosphorylation of APC subunits is required for Cdc20 mediated activation by of the APC/C at the metaphase anaphase transition (Kramer et al., 2000). While the kinases responsible for phosphorylation in vivo have not been determined with certainty, both Plk1 and Cyclin B:Cdc2 have been implicated in this process.

Set (3 results from a total of 3)

Identifier: R-HSA-5246650
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-4791256
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-174056
Species: Homo sapiens
Compartment: cytosol

Complex (4 results from a total of 40)

Identifier: R-HSA-174081
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-6781912
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-174212
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-3788733
Species: Homo sapiens
Compartment: nucleoplasm

Interactor (2 results from a total of 2)

Identifier: Q8IVL1
Species: Homo sapiens
Primary external reference: UniProt: Q8IVL1
Identifier: Q8J025
Species: Homo sapiens
Primary external reference: UniProt: Q8J025

Icon (4 results from a total of 4)

APC

Species: Homo sapiens
Curator: Karen Rothfels
Designer: Cristoffer Sevilla
APC icon
Adenomatous polyposis coli protein
Species: Homo sapiens
Also known as Anaphase-promoting complex is an E3 ubiquitin ligase that marks target cell cycle proteins for degradation by the 26S proteasome
Species: Homo sapiens
Curator: Karen Rothfels
Designer: Cristoffer Sevilla
AMER1 icon
APC membrane recruitment protein 1
Species: Homo sapiens
Curator: Karen Rothfels
Designer: Cristoffer Sevilla
Destruction complex icon
A cytoplasmic protein complex containing glycogen synthase kinase-3-beta (GSK-3-beta), the adenomatous polyposis coli protein (APC), and the scaffolding protein axin, among others; phosphorylates beta-catenin, targets it for degradation by the proteasome
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