Inhibiting transient protein-protein interactions: lessons from the Cdc25 protein tyrosine phosphatases.
Transient protein-protein interactions have key regulatory functions in many of the cellular processes that are implicated in cancerous growth, particularly the cell cycle. Targeting these transient interactions as therapeutic targets for anticancer drug development seems like a good idea, but it is not a trivial task. This Review discusses the issues and difficulties that are encountered when considering these transient interactions as drug targets, using the example of the cell division cycle 25 (Cdc25) phosphatases and their cyclin-dependent kinase (CDK)-cyclin protein substrates.
Rudolph
Johannes
J
Department of Biochemistry, Duke University Medical Center, BOX 3813, LSRC Building, Room C125, Durham, North Carolina 27710, USA. johannes@alum.mit.edu
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D018844:Cyclin-Dependent Kinases / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000201:enzymology; D011485:Protein Binding / Q000187:drug effects; D020836:Protein Structure, Quaternary; D015398:Signal Transduction / Q000502:physiology*; D020687:cdc25 Phosphatases / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
D004791:Enzyme Inhibitors; D018844:Cyclin-Dependent Kinases; D020687:cdc25 Phosphatases