Adaptation of the ubiquitin-proteasome proteolytic pathway in cancer cachexia

The ubiquitin-proteasome proteolytic pathway is of major importance in the breakdown of skeletal muscle proteins. The first step in this pathway is th e covalent attachment of polyubiquitin chains to the targeted protein. Poly ubiquitinylated proteins are then recognized and degraded by the 26S protea some complex. In this review, we critically analyze recent findings in the regulation of ubiquitinylation of protein substrates and of their subsequen t proteasome-dependent degradation in animal models of cancer cachexia. In particular, we discuss the influence of various mediators (anorexia, hormon es, prostaglandins, cytokines, and proteolysis-inducing factor) in signalin g the activation of ubiquitin-proteasome proteolysis in skeletal muscle. Th ese findings have lead to new concepts that are starting to be used for pre venting cachexia in cancer and other wasting diseases.