Harnessing the Ubiquitination Machinery to Target the Degradation of Specific Cellular Proteins

• Published in: Molecular cell Vol. 6; no. 3; pp. 751 - 756
• Main Authors: Zhou, Pengbo, Bogacki, Robert, McReynolds, Lisa, Howley, Peter M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2000
• Subjects: Animals; beta-Transducin Repeat-Containing Proteins; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; F-Box Proteins; F-Box-WD Repeat-Containing Protein 7; Female; Gene Expression Regulation, Enzymologic; GTP-Binding Proteins - metabolism; Humans; Ligases - genetics; Ligases - metabolism; Mammals; Molecular Biology - methods; Nuclear Proteins - metabolism; Osteosarcoma; Plasmids; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Retinoblastoma Protein - metabolism; Retinoblastoma-Like Protein p107; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Substrate Specificity - genetics; Tumor Cells, Cultured; ubiquitin; Ubiquitin-Protein Ligases; Ubiquitins - metabolism; Uterine Cervical Neoplasms
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/S1097-2765(00)00074-5

The functional characterization of a specific gene, or its protein product, often relies on assessing the consequences of its elimination, usually accomplished by gene knockout, ribozyme, antisense, or RNA-mediated interference (RNAi) technologies. The selective degradation of cellular proteins is mediated primarily by the ubiquitin-proteasome pathway. Manipulation of the ubiquitin-dependent proteolytic machinery to eliminate specific gene products at the protein level has been previously attempted with some success in vitro; however, the in vivo efficacy of this approach has not yet been achieved. Here we report successful engineering of the substrate receptor of a major ubiquitin-proteolytic machinery to direct the degradation of otherwise stable cellular proteins both in yeast and in mammalian cells.