Oncogenic aberrations of cullin-dependent ubiquitin ligases.

Accumulating evidence points to a key role of the ubiquitin-proteasome pathway in oncogenesis. Aberrant proteolysis of substrates involved in cellular processes such as the cell division cycle, gene transcription, the DNA damage response and apoptosis has been reported to contribute significantly to neoplastic transformation. Cullin-dependent ubiquitin ligases (CDLs) form a class of structurally related multisubunit enzymes central to the ubiquitin-mediated proteolysis of many important biological substrates. In this review, we describe the role of CDLs in the ubiquitinylation of cancer-related substrates and discuss how altered ubiquitinylation by CDLs may contribute to tumor development.