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Sci. STKE, 3 October 2000
Vol. 2000, Issue 52, p. tw11
[DOI: 10.1126/stke.2000.52.tw11]


Cachexia Cachexia and NF-{kappa}B

Patients with chronic diseases such as cancer and AIDS often develop cachexia, a life-threatening disorder characterized by extensive weight loss and degeneration of skeletal muscle. The cytokine tumor necrosis factor (TNF) is a critical mediator of the muscle wasting in cachexia, but little else is known about its molecular pathogenesis. Two reports discuss the role that the transcription factor NF-{kappa}B, a key component in the inflammatory response induced by TNF, plays in this disease. Guttridge et al. (see the Perspective by Tisdale) show that NF-{kappa}B in muscle cells suppresses the activity of MyoD, a transcription factor needed for muscle repair, by reducing the levels of MyoD messenger RNA. Lee et al. describe the phenotype of knockout mice lacking the A20 protein, an inhibitor of signaling through NF-{kappa}B. The mice show severe inflammation and cachexia and die prematurely. The results suggest an inhibitory physiological role for A20 early in the signaling pathway leading from the TNF receptor to the activation of NF-{kappa}B. Paradoxically, A20 also appears to protect cells from programmed cell death.

Guttrudge, D.C., Mayo, M.W., Madrid, L.V., Wang, C.-Y., and Baldwin, A.S., Jr. (2000) NF-{kappa}B-induced loss of MyoD messenger RNA: Possible role in muscle decay and cachexia. Science 289: 2363-2366. [Abstract] [Full Text]

Tisdale, M.J. (2000) Protein loss in cancer cachexia. Science 289: 2293-2294. [Abstract] [Full Text]

Lee, E.G., Boone, D.L., Chai, S., Libby, S.L., Chien, M., Lodolce, J.P., and Ma, A. (2000) Failure to regulate TNF-induced NF-{kappa}B and cell death responses in A20-deficient mice. Science 289: 2350-2354. [Abstract] [Full Text]

Citation: Cachexia and NF-{kappa}B. Sci. STKE 2000, tw11 (2000).

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