scholarly journals Where is APC going?

2001 ◽  
Vol 154 (6) ◽  
pp. 1105-1110 ◽  
Author(s):  
Yuko Mimori-Kiyosue ◽  
Shoichiro Tsukita
Keyword(s):  
Tumor Suppressor ◽  
Signaling Pathway ◽  
Adenomatous Polyposis Coli ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Apc Protein

Adenomatous polyposis coli (APC) protein has been thought to function as a tumor suppressor through its involvement in the Wnt/β-catenin signaling pathway. However, its connections to the cytoskeleton and microtubules in particular are becoming apparent, and the discovery of these new functions for APC is leading to a reevaluation of its role not only in tumorigenesis, but also in normal physiology.

scholarly journals Adenomatous Polyposis Coli Tumor Suppressor Protein Has Signaling Activity in Xenopus laevis Embryos Resulting in the Induction of an Ectopic Dorsoanterior Axis

1997 ◽  
Vol 136 (2) ◽  
pp. 411-420 ◽  
Author(s):  
Kris Vleminckx ◽  
Ellen Wong ◽  
Kathy Guger ◽  
Bonnee Rubinfeld ◽  
Paul Polakis ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Suppressor ◽  
Adenomatous Polyposis Coli ◽  
Protein A ◽  
Homeobox Gene ◽  
Xenopus Embryo ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Human Colon Cancer ◽  
Signaling Activity

Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene are linked to both familial and sporadic human colon cancer. So far, a clear biological function for the APC gene product has not been determined. We assayed the activity of APC in the early Xenopus embryo, which has been established as a good model for the analysis of the signaling activity of the APC-associated protein β-catenin. When expressed in the future ventral side of a four-cell embryo, full-length APC induced a secondary dorsoanterior axis and the induction of the homeobox gene Siamois. This is similar to the phenotype previously observed for ectopic β-catenin expression. In fact, axis induction by APC required the availability of cytosolic β-catenin. These results indicate that APC has signaling activity in the early Xenopus embryo. Signaling activity resides in the central domain of the protein, a part of the molecule that is missing in most of the truncating APC mutations in colon cancer. Signaling by APC in Xenopus embryos is not accompanied by detectable changes in expression levels of β-catenin, indicating that it has direct positive signaling activity in addition to its role in β-catenin turnover. From these results we propose a model in which APC acts as part of the Wnt/β-catenin signaling pathway, either upstream of, or in conjunction with, β-catenin.

scholarly journals The Adenomatous Polyposis Coli Protein Is Required for the Formation of Robust Spindles Formed in CSF Xenopus Extracts

2004 ◽  
Vol 15 (6) ◽  
pp. 2978-2991 ◽  
Author(s):  
Dina Dikovskaya ◽  
Ian P. Newton ◽  
Inke S. Näthke
Keyword(s):  
Adenomatous Polyposis Coli ◽  
Chromosomal Instability ◽  
Adenomatous Polyposis ◽  
Mitotic Spindles ◽  
Polyposis Coli ◽  
Adenomatous Polyposis Coli Protein ◽  
Microtubule Binding ◽  
Microtubule Polymerization ◽  
Large N ◽  
Apc Protein

Mutations in the adenomatous polyposis coli (APC) protein occur early in colon cancer and correlate with chromosomal instability. Here, we show that depletion of APC from cystostatic factor (CSF) Xenopus extracts leads to a decrease in microtubule density and changes in tubulin distribution in spindles and asters formed in such extracts. Addition of full-length APC protein or a large, N-terminally truncated APC fragment to APC-depleted extracts restored normal spindle morphology and the intact microtubule-binding site of APC was necessary for this rescue. These data indicate that the APC protein plays a role in the formation of spindles that is dependent on its effect on microtubules. Spindles formed in cycled extracts were not sensitive to APC depletion. In CSF extracts, spindles predominantly formed from aster-like intermediates, whereas in cycled extracts chromatin was the major site of initial microtubule polymerization. These data suggest that APC is important for centrosomally driven spindle formation, which was confirmed by our finding that APC depletion reduced the size of asters nucleated from isolated centrosomes. We propose that lack of microtubule binding in cancer-associated mutations of APC may contribute to defects in the assembly of mitotic spindles and lead to missegregation of chromosomes.

Evidence for the involvement of adenomatous polyposis coli (APC) protein in maintaining cellular distributions of α3β4 nicotinic receptors

2011 ◽  
Vol 489 (2) ◽  
pp. 105-109
Author(s):  
Tulaya Potaros ◽  
Srichan Phornchirasilp ◽  
Susan B. McKay ◽  
Tatiana F. González-Cestari ◽  
R. Thomas Boyd ◽  
...  
Keyword(s):  
Adenomatous Polyposis Coli ◽  
Nicotinic Receptors ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Apc Protein
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