标题: Out with the active ?-catenin [打印本页] 作者: 杨柳 时间: 2009-3-6 09:01 标题: Out with the active ?-catenin
Wnt signals are converted into changes in gene expression by ?-catenin, which turns on the TCF/Lef transcription factors. In a search for nuclear ?-catenin–interacting proteins, the authors picked up RanBP3 in a pull-down assay. As RanBP3 is a cofactor for CRM1-mediated nuclear export, the logical next step was to look at ?-catenin export. $ O; u. x& }+ z5 N. o1 v& V+ d3 x+ S* t5 u& m0 C% U
Nuclear levels of total ?-catenin were not affected by RanBP3, but the authors found a more specific target. A very small, almost invisible, fraction of ?-catenin〞the active dephosporylated form〞relocated from the nucleus to the cytoplasm upon RanBP3 overexpression. Only by using tumor cell lines with unusually high levels of active ?-catenin were the authors even able to detect this pool in situ.' U; V5 G4 B2 z- @9 M6 d% S% o
0 M1 [8 j0 `" R. r$ D3 l! eAs a result of the export, Wnt signals were unable to activate their transcription programs. By contrast, fly embryos lacking active RanBP3 had developmental defects associated with too much Wnt (presumably from too much active nuclear ?-catenin). RanBP3 overexpression in frog embryos had the reverse effect. The authors do not yet know whether endogenous RanBP3 levels increase to inhibit Wnt signaling, as required during differentiation, for example. . f& u) H3 }7 ^5 l6 u `( @9 y
RanBP3 is a cofactor for the CRM1 exporter, but ?-catenin export was independent of CRM1. Perhaps RanBP3 accompanies ?-catenin through a different export pathway. Alternatively, RanBP3 might compete for DNA binding sites that retain active ?-catenin in the nucleus.(A highly active subset of ?-catenin is s)作者: beautylive 时间: 2015-6-6 12:27