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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Molecular chaperones affect GTP cyclohydrolase I mutations in dopa-responsive dystonia.

Unstable GTP cyclohydrolase I ( GCH) mutations in dopa-responsive dystonia (DRD) can exert a dominant-negative effect in the HeLa cell model, but in a batch of cells this effect could not be shown. Through differential display, we found a higher Hsc70 expression in the non-dominant-negative cells. We further demonstrated that ectopic expression of Hsp40/Hsp70 stabilized the GCH mutant G201E. Moreover, Hsp90 inhibitor geldanamycin destroyed the wild-type GCH level, and heat shock increased the synthesis of GCH protein. Therefore, the dominant-negative effect produced by unstable proteins would be susceptible to the status of molecular chaperones, which could be the modifying genes and therapeutic targets for DRD and other genetic diseases.[1]

References

  1. Molecular chaperones affect GTP cyclohydrolase I mutations in dopa-responsive dystonia. Hwu, W.L., Lu, M.Y., Hwa, K.Y., Fan, S.W., Lee, Y.M. Ann. Neurol. (2004) [Pubmed]
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