scholarly journals Adenomatous polyposis coli protein (APC)-independent regulation of β-catenin/Tcf-4 mediated transcription in intestinal cells

1999 ◽  
Vol 344 (2) ◽  
pp. 565-570 ◽  
Author(s):  
Josep BAULIDA ◽  
Eduard BATLLE ◽  
Antonio GARCÍA DE HERREROS
Keyword(s):  
Adenomatous Polyposis Coli ◽  
Transcriptional Activity ◽  
Intestinal Cell ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Binding Assays ◽  
Adenomatous Polyposis Coli Protein ◽  
Kinase C ◽  
Intestinal Cell Lines

Alterations in the transcriptional activity of the β-catenin-Tcf complex have been associated with the earlier stages of colonic transformation. We show here that the activation of protein kinase C by the phorbol ester PMA in several intestinal cell lines increases the levels of β-catenin detected in the nucleus and augments the transcriptional activity mediated by β-catenin. The response to PMA was not related to modifications in the cytosolic levels of β-catenin and was observed not only in cells with wild-type adenomatous polyposis coli protein (APC) but also in APC-deficient cells. Binding assays in vitro revealed that PMA facilitates the interaction of the β-catenin with the nuclear structure. Our results therefore show that β-catenin-mediated transcription can be regulated independently of the presence of APC.

scholarly journals Adenomatous polyposis coli protein nucleates actin assembly and synergizes with the formin mDia1

2010 ◽  
Vol 189 (7) ◽  
pp. 1087-1096 ◽  
Author(s):  
Kyoko Okada ◽  
Francesca Bartolini ◽  
Alexandra M. Deaconescu ◽  
James B. Moseley ◽  
Zvonimir Dogic ◽  
...  
Keyword(s):  
Adenomatous Polyposis Coli ◽  
Microtubule Dynamics ◽  
Actin Dynamics ◽  
Adenomatous Polyposis ◽  
Actin Assembly ◽  
Polyposis Coli ◽  
Adenomatous Polyposis Coli Protein ◽  
Cell Protrusion

The tumor suppressor protein adenomatous polyposis coli (APC) regulates cell protrusion and cell migration, processes that require the coordinated regulation of actin and microtubule dynamics. APC localizes in vivo to microtubule plus ends and actin-rich cortical protrusions, and has well-documented direct effects on microtubule dynamics. However, its potential effects on actin dynamics have remained elusive. Here, we show that the C-terminal “basic” domain of APC (APC-B) potently nucleates the formation of actin filaments in vitro and stimulates actin assembly in cells. Nucleation is achieved by a mechanism involving APC-B dimerization and recruitment of multiple actin monomers. Further, APC-B nucleation activity is synergistic with its in vivo binding partner, the formin mDia1. Together, APC-B and mDia1 overcome a dual cellular barrier to actin assembly imposed by profilin and capping protein. These observations define a new function for APC and support an emerging view of collaboration between distinct actin assembly–promoting factors with complementary activities.

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.

scholarly journals The Adenomatous Polyposis Coli Protein Contributes to Normal Compaction of Mitotic Chromatin

PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e38102 ◽  
Author(s):  
Dina Dikovskaya ◽  
Guennadi Khoudoli ◽  
Ian P. Newton ◽  
Gaganmeet S. Chadha ◽  
Daniel Klotz ◽  
...  
Keyword(s):  
Adenomatous Polyposis Coli ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Adenomatous Polyposis Coli Protein ◽  
Mitotic Chromatin

scholarly journals A metabolic switch controls intestinal differentiation downstream of Adenomatous polyposis coli (APC)

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Imelda T Sandoval ◽  
Richard Glenn C Delacruz ◽  
Braden N Miller ◽  
Shauna Hill ◽  
Kristofor A Olson ◽  
...  
Keyword(s):  
Cell Fate ◽  
Adenomatous Polyposis Coli ◽  
Normal Development ◽  
Intestinal Cell ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Pyruvate Metabolism ◽  
Metabolic Switch ◽  
Intestinal Differentiation ◽  
Mitochondrial Pyruvate Carrier

Elucidating signaling pathways that regulate cellular metabolism is essential for a better understanding of normal development and tumorigenesis. Recent studies have shown that mitochondrial pyruvate carrier 1 (MPC1), a crucial player in pyruvate metabolism, is downregulated in colon adenocarcinomas. Utilizing zebrafish to examine the genetic relationship between MPC1 and Adenomatous polyposis coli (APC), a key tumor suppressor in colorectal cancer, we found that apc controls the levels of mpc1 and that knock down of mpc1 recapitulates phenotypes of impaired apc function including failed intestinal differentiation. Exogenous human MPC1 RNA rescued failed intestinal differentiation in zebrafish models of apc deficiency. Our data demonstrate a novel role for apc in pyruvate metabolism and that pyruvate metabolism dictates intestinal cell fate and differentiation decisions downstream of apc.

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