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Although the cellular adhesion molecule CD44 is involved in processes ranging from lymphocyte homing to tumor metastasis, it has remained unclear how CD44 transduces the intracellular signals required for such a broad range of activities. On page 755, Okamoto et al. propose a surprising mechanism for CD44 signal transduction: a cytoplasmic domain is cleaved from the protein, after which it translocates to the nucleus and acts directly as a transcriptional regulator.7 i* a3 {5 L9 e! ~6 z" h( n
+ T( p, n! U- @8 w2 H: F# {7 \+ Y" APrevious work demonstrated that the extracellular domain of CD44 can be cleaved by membrane-associated proteases, regulating the interaction between CD44 and the extracellular matrix. Okamoto et al. identified a subsequent proteolytic cleavage that releases a fragment of the CD44 intracellular domain (CD44ICD). This fragment translocates to the nucleus, where it activates transcription from the TPA-responsive transcriptional regulation elements found in front of a variety of cellular genes. CD44ICD overexpression also induces CD44 mRNA expression, suggesting a feedback mechanism to regulate CD44 levels. In addition to illuminating the mechanism of CD44 signaling, the new work provides the first example of an adhesion molecule using a type of signal transduction first described for Notch, in which a cleavage fragment of a membrane receptor serves as a transcriptional activator.(CD44 can enter and signal in the nucleus) |
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发表于 2009-3-5 23:46
发表于 2009-11-15 21:34
