Title | Targeted protein degradation. |
Publication Type | Journal Article |
Year of Publication | 2005 |
Authors | Zhou P |
Journal | Curr Opin Chem Biol |
Volume | 9 |
Issue | 1 |
Pagination | 51-5 |
Date Published | 2005 Feb |
ISSN | 1367-5931 |
Keywords | F-Box Proteins, Humans, Proteasome Endopeptidase Complex, Protein Engineering, Recombinant Fusion Proteins, Ubiquitins |
Abstract | The ubiquitin-proteasome pathway plays a major role in cellular protein destruction and regulates fundamental cellular processes such as the cell cycle, cell signaling, and development. By altering the substrate recognition of ubiquitin-protein ligases, their robust proteolytic activity can be re-directed to recruit and accelerate the degradation of other cellular targets. Two approaches have been applied for targeted proteolysis: one entails designing a chimeric substrate receptor for recruitment of the target protein, the other involves the construction of peptide-small-molecule hybrids that bridge the interaction between the intended target and the substrate receptor of the known ubiquitin-protein ligases. The engineered ubiquitin-proteolytic apparatus operates at the post-translational level, and thus provides a new tool of reverse genetics to dissect complicated protein functions at a higher resolution than knockout or knockdown approaches functioning at the level of DNA or RNA. It also sheds light on novel therapeutic strategies for the amelioration of human disease. |
DOI | 10.1016/j.cbpa.2004.10.012 |
Alternate Journal | Curr Opin Chem Biol |
PubMed ID | 15701453 |
Grant List | 5R33 CA92792 / CA / NCI NIH HHS / United States |
Related Lab:
Related Faculty:
Pengbo Zhou, Ph.D.