First Author | Meng X | Year | 2001 |
Journal | J Biol Chem | Volume | 276 |
Issue | 43 | Pages | 40113-9 |
PubMed ID | 11477086 | Mgi Jnum | J:119466 |
Mgi Id | MGI:3702247 | Doi | 10.1074/jbc.M105317200 |
Citation | Meng X, et al. (2001) Suppressor of fused negatively regulates beta-catenin signaling. J Biol Chem 276(43):40113-9 |
abstractText | Suppressor of fused (Su(fu)) is a negative regulator of the Hedgehog signaling pathway that controls the nuclear-cytoplasmic distribution of Gli/Ci transcription factors through direct protein-protein interactions. We show here that Su(fu) is present in a complex with the oncogenic transcriptional activator beta-catenin and functions as a negative regulator of T-cell factor (Tcf)-dependent transcription. Overexpression of Su(fu) in SW480 (APC(mut)) colon cancer cells in which beta-catenin protein is stabilized leads to a reduction in nuclear beta-catenin levels and in Tcf-dependent transcription. This effect of Su(fu) overexpression can be blocked by treatment of these cells with leptomycin B, a specific inhibitor of CRM1-mediated nuclear export. Overexpression of Su(fu) suppresses growth of SW480 (APC(mut)) tumor cells in nude mice. These observations indicate that Su(fu) negatively regulates beta-catenin signaling and that CRM-1-mediated nuclear export plays a role in this regulation. Our results also suggest that Su(fu) acts as a tumor suppressor. |