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Abstract:
Beta-catenin is a critical signaling molecule that participates in differentiation and proliferation pathways. Beta-catenin binds the HMG-box transcription factor LEF-l, to directly regulate gene transcription. The tumor suppressor adenomatous polyposis coli (APC) gene product has been reported to associate with beta-catenin and effect its down- regulation by an unknown mechanism. We hypothesize that APC helps target beta-catenin to proteasomal degradation. We tested our hypotheses in vivo by transient transfections of colon cancer cells with various APC deletion constructs, followed by treatment with proteasome-specific inhibitors. The LEF-reporters TOPFLASH and FOPFLASH were used to demonstrate a role for APC in regulating beta-catenin-LEF signaling via the ubiquitin- proteasome pathway. Surprisingly, lithium (that inhibits GSK3 beta also) was found not to reverse the ability of APC to down-regulate LEF signaling.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Annual rept. 15 Jun 97-14 Jun 98 |
| Pages: |
15 |
| Report Date: |
JUL 1998 |
| Contract Number: |
DAMD17-94-J-4171 |
| Report Number: |
A451073 |
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