|
  
- 积分
- 0
- 威望
- 0
- 包包
- 3465
|
Birchmeier/Macmillan5 M+ O! A- L6 Y
& ?/ G- Y6 x9 Y' |2 t. g- X& A
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)." }. p, l) x4 i( n0 W, \
( |+ J9 R1 i$ d1 T
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.
' s+ g4 C0 v+ \2 H3 ]/ Z; X; W# l6 V# Z6 A3 I# U' ~3 D
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./ V" i9 G0 { p. b0 z4 N" v
& Q; B& J9 Q/ wBirchmeier 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.+ M7 }: T% `# Q U1 Q8 {
e6 n; f) x% kDisruption 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:* s6 g$ ?$ a# U) _ n* S, m
) Y0 c2 M' `( h" m e* c3 JFujita, 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
