Regulation of the phosphorylation and nuclear import and export of β-catenin by APC and its cancer-related truncated form.

Abstract:

:We report the first direct analysis of the endogenous β-catenin phosphorylation activity in colon cancer SW480 cells. By comparing parental SW480 cells that harbor a typical truncated adenomatous polyposis coli (APC) form, cells expressing full-length APC and APC-depleted cells, we provide the formal demonstration that APC is necessary for β-catenin phosphorylation, both for priming of the protein at residue serine 45 and for the subsequent phosphorylation of residues 33, 37 and 41. Truncated APC still sustains a surprisingly high phosphorylation activity, which requires the protein to bind to β-catenin through the APC 20-amino-acid (20AA) repeats, thus providing a biochemical explanation for the precise truncations found in cancer cells. We also show that most of the β-catenin phosphorylation activity is associated with a dense insoluble fraction. We finally examine the impact of full-length and truncated APC on β-catenin nuclear transport. We observe that β-catenin is transported much faster than previously thought. Although this fast translocation is largely insensitive to the presence of wild-type or truncated APC, the two forms appear to limit the pool of β-catenin that is available for transport, which could have an impact on β-catenin nuclear activities in normal and cancer cells.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Wang L,Liu X,Gusev E,Wang C,Fagotto F

doi

10.1242/jcs.131045

subject

Has Abstract

pub_date

2014-04-15 00:00:00

pages

1647-59

issue

Pt 8

eissn

0021-9533

issn

1477-9137

pii

jcs.131045

journal_volume

127

pub_type

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