标题: Coming undone at the seams [打印本页] 作者: 杨柳 时间: 2009-3-6 00:18 标题: Coming undone at the seams
Birchmeier/Macmillan ; S! `! D) L6 p1 x1 [8 Q - E* i9 T1 m1 [' c' P, OCells 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).8 ]8 d- V0 n2 S I4 `5 X5 M. J6 Q8 d
6 P& K& o8 w4 K- m/ lBirchmeier'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. ( g4 ]+ Y: l! G6 m. y ) U; g" u8 R9 @! t. N/ nIn 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.( \7 ~$ Y, {' H
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Birchmeier 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. / k3 e* W+ H8 M8 D& v4 R" R8 G7 N1 Z! B: x* [. G7 R: M; t/ U
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: 8 s' p- o2 n' A+ w& l/ a7 g( b' j. P( z 5 C- [! Q1 L/ G: UFujita, Y., et al., 2002. Nat. Cell Biol. 10.1038/ncb758.(Overexpression of Hakai (right) increase)作者: 兔兔 时间: 2015-6-6 09:01