A New APC-like Gene Involved in Regulation of B-catenin/LEF
Abstract
A second adenomatous polyposis coli (APC)-like gene, APC2, was recently described and localized to chromosome 19. We have now fine mapped APC2 to a small region of chromosome 19p13.3 containing markers D19S883 and WI-19632, a region commonly lost in a variety of cancers. APC2 is expressed in many different tissues and cell lines including brain, breast, colon, and ovary. Endogenous APC2 is diffusely distributed in the cytoplasm and co-localizes with both the Golgi apparatus and actin filaments. Unlike APC, APC2 and beta-catenin remained associated with actin filaments following treatment with the actin-disrupting agent, cytochalasin D. In addition, APC2 co-localizes with beta-catenin and actin filaments at the membrane of SKBR3 cells upon retinoic acid treatment. Like APC, APC2 has the ability to down-regulate beta-catenin signaling and is sensitive to the PKC inhibitor bisindoylmaleimide. APC2 is more sensitive than APC to inhibition of GSK3 with LiCl and, unlike APC, can inhibit the signaling activity of a S37A mutant form of beta-catenin. These results suggest that APC2 is involved in actin associated events and could influence cell motility through interaction with actin filaments as well as functioning independently or in cooperation with APC to down- regulate beta-catenin signaling.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA385511
Entities
People
- Christy Jarrett
Organizations
- Georgetown University