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Sci. STKE, 5 December 2000
Vol. 2000, Issue 61, p. tw9
[DOI: 10.1126/stke.2000.61.tw9]


Apoptosis Cell Death by PACT

The interferon-regulated double stranded (ds)RNA-activated protein kinase (PKR) is activated by viral dsRNA. Patel et al. characterized a recently discovered cellular protein termed PACT (PKR activating) that activates PKR in the absence of viral infection. Overexpression of PACT in cells resulted in increased apoptosis in the absence of stress, suggesting that the transfected cells were sensitized for apoptosis. PACT overexpression in stressed cells also greatly increased apoptosis. This effect appeared to be largely PKR-dependent, because in PKR-null cells overexpression of PACT did not stimulate apoptosis. Endogenous PACT coprecipitated with PKR in a stress-dependent manner, indicating that the proteins can interact when present at physiologically relevant levels. Time-course experiments in arsenite-treated cells revealed PACT phosphorylation concomitant with PACT-PKR association and PKR activation; however, whether PACT is phosphorylated by PKR is unclear. The authors suggest that although viral activation of PKR leads to reduced protein synthesis, inhibition of proliferation, and (in some cases) apoptosis, PACT may function in virus-independent cellular apoptosis.

Patel, C.V., Handy, I., Goldsmith, T., and Patel, R.C. (2000) PACT, a stress-modulated cellular activator of interferon-induced double-stranded RNA-activated protein kinase, PKR. J. Biol. Chem. 275: 37993-37998. [Abstract] [Full Text]

Citation: Cell Death by PACT. Sci. STKE 2000, tw9 (2000).

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