MOLECULAR BIOLOGY: Turning on a Helicase

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Science  15 Feb 2002:
Vol. 295, Issue 5558, pp. 1197c
DOI: 10.1126/science.295.5558.1197c

One approach to dealing with the problem of cells that escape from the network of controls regulating development and differentiation is to attempt to direct such cells toward a terminally differentiated state, perhaps with the hope of encouraging them to undergo apoptosis voluntarily. A combination of interferon-β and a protein kinase C activator has been shown to shift human melanoma cells into such a state.

Kang et al. have carried out an analysis of a gene, mda-5, whose expression is increased by this treatment; it appears to encode a RNA helicase (which would unwind double helices of RNA) on the basis of sequence similarities and an RNA-dependent ATPase activity. Expression of this gene appears to mimic the effect of interferon, inhibiting growth of these melanoma cells in vitro. Two other attributes of this protein, although as yet unsubstantiated, offer tantalizing hints at linkages to other degradative pathways. First, MDA-5 contains a caspase-recruitment domain (CARD), which is common to many components involved in initiating and regulating apoptosis. Second, other helicases in the MDA-5 group contain RNase III motifs, a signature of the enzymes (such as DICER) involved in RNA interference—mediated gene silencing. — GJC

Proc. Natl. Acad. Sci. U.S.A. 99, 637 (2002).

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