|
  
- 积分
- 0
- 威望
- 0
- 包包
- 3465
|
Birchmeier/Macmillan2 T9 S& ?/ T* s$ P& h
5 f+ O* M9 B+ }" E
Cells come unglued and transition to a more motile phenotype with the help of an E3 ligase, according to new results from Walter Birchmeier and colleagues (Max-Delbrück-Center for Molecular Medicine, Berlin, Germany).0 K7 ]7 ?7 S* m5 p* d
% c( O4 T6 ~2 O g: _Birchmeier's study focused on cadherins, adhesion molecules that act as anchors via a catenin link to the actin cytoskeleton. During embryogenesis and carcinoma progression, disruption of cadherin-mediated adhesion between epithelial cells helps them make the transition to a more mobile, mesenchymal phenotype. This transition involves endocytosis of cadherin and catenin molecules following phosphorylation by tyrosine kinases such as Src or c-Met.
6 r2 z+ R2 r3 }$ P; Q( ?0 Y" _6 ^, B) G
In the new study, Birchmeier identified a cadherin-binding protein, Hakai, that promotes endocytosis of the cadherin complex, leading to disruption of cell adhesion. Hakai binds to E-cadherin, the prototypical member of the cadherin family, in a phosphorylation-dependent manner. It also competes with other adhesion molecules, such as p120ctn, for E-cadherin binding.
2 s* }) X4 k/ {5 ]! V
1 Y; o- R) m2 A4 ~# a. FBirchmeier says that "Hakai smelled of degradation," as it has sequence similarity to c-Cbl, an E3 ligase that ubiquitinates phosphorylated tyrosine kinase receptors and prompts their internalization and degradation. Hakai, which is Japanese for destruction, increases ubiquitination of the E-cadherin complex, particularly when E-cadherin is phosphorylated by Src or in response to growth factors. C$ z \0 W: {3 f1 v
# b: }+ W- n6 `! x
Disruption of cell adhesion by Hakai causes cell scattering, similar to that observed during the transition to a mesenchymal phenotype. Birchmeier now plans to test whether Hakai's motility-promoting properties are used by tumor cells to trigger invasion and metastasis.Reference:
/ o3 D3 H4 t- H$ u# R4 k& P+ [1 n. q+ J+ M2 b6 T8 k
Fujita, Y., et al., 2002. Nat. Cell Biol. 10.1038/ncb758.(Overexpression of Hakai (right) increase) |
|
发表于 2009-3-6 00:18
发表于 2015-6-6 09:01
