Ubiquitination-dependent regulation of signaling receptors in cancer.

Ubiquitination of signaling cell surface receptors is a key mechanism regulating the availability of these receptors to interact with extracellular ligands. Accordingly, this regulation determines the sensitivity of cells to the humoral and locally secreted regulators of cell function, proliferation, and viability. Alterations in receptor ubiquitination and degradation are often encountered in cancers. Malignant cells utilize modified ubiquitination of signaling receptors to augment or attenuate signaling pathways on the basis of whether the outcome of this signaling is conducive or not for tumor growth and survival. These mechanisms as well as their significance for the treatment of human cancers are discussed.