Lethal Weight Loss: The Focus Shifts to Signal Transduction

Kevin J. Tracey^*

North Shore-Long Island Jewish Research Institute, Manhasset, NY 11020, USA.

Summary: A hallmark of life-threatening disease in vertebrates is cachexia, a syndrome of weight loss with progressive erosion of body protein. Tumor necrosis factor (TNF) and other endogenously derived factors are sufficient to mediate the pathophysiology of cachexia in vivo, but the downstream signaling pathways have remained a mystery until recently. Tracey describes the involvement of the stress-activated protein kinase p38 and the transcriptional regulators nuclear factor kappa B and peroxisome proliferator-activated receptor gamma coactivator-1 in causing alterations in myocytes and skeletal muscle physiology. Furthermore, soluble factors including TNF and proteolysis-inducing factor may enhance protein degradation through the ubiquitin-proteosome pathway.

*Contact information. E-mail: kjtracey{at}sprynet.com

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