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Methylation Outside the Nucleus

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Science  20 May 2005:
Vol. 308, Issue 5725, pp. 1089
DOI: 10.1126/science.308.5725.1089c

Ezh2 is a member of the polycomb group of proteins and functions in development by catalyzing the methylation of lysine residues on histone proteins, thereby causing changes in gene expression. However, Ezh2 exists in the cytoplasm as well as the nucleus, and Su et al. have explored whether the enzyme might have functions apart from its role in modifying chromatin structure. Ezh2 has been reported to associate with the guanine nucleotide exchange factor Vav1, which is an important component of T cell signaling and mediator of changes in actin polymerization in response to stimulation of the T cell receptor (TCR). T cells lacking Ezh2 were defective in TCR-induced actin polymerization and showed an impaired proliferative response. Similarly, fibroblasts lacking Ezh2 showed decreased actin polymerization in response to platelet-derived growth factor, and this deficiency could be rescued by expressing a cytoplasmically localized form of Ezh2. The methylation target of Ezh2 is not known but appears to lie between TCR activation and activation of the guanosine triphosphate Cdc42; Vav1, though, appears not be modified by Ezh2. These findings indicate that posttranslational modification by methylation has key regulatory roles outside of the nucleus, with implications for immune responses to the TCR and cancer biology, where increased expression of Ezh2 in cancer cells is associated with increased metastatic capacity. — LBR

Cell 121, 426 (2005).

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