Abstract: Dimerization and oligomerization of proteins are general biological control mechanisms that contribute to the activation of cell membrane receptors, transcription factors, vesicle fusion proteins, and other classes of intra- and extracellular proteins. We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins. In principle, any two target proteins can be induced to associate by treating the cells or organisms that harbor them with cell permeable, synthetic ligands. To illustrate the practice of this invention, we have induced: (1) the intracellular aggregation of the cytoplasmic tail of the .zeta.
Type:
Grant
Filed:
September 16, 1998
Date of Patent:
May 16, 2000
Assignees:
Board of Trustees of Leland S, Stanford, Jr. University, President and Fellows of Harvard College
Inventors:
Gerald R. Crabtree, Stuart L. Schreiber, David M. Spencer, Thomas J. Wandless, Steffan N. Ho, Peter Belshaw
Abstract: Methods and compositions are provided for modified cells, where a chimeric protein consisting of a ligand binding domain fused to an action domain is employed which initiates a signal which activates a biological process: transcription of at least one gene, usually a second construct introduced into the host cells; exocytosis; or an extracellular process. The second construct optimally present provides for a promoter which responds to a transcriptional activation action domain to provide for transcription, when an appropriate ligand binds to the ligand binding domain. Exemplary of the system is the use of an FKBP/CD3.zeta. or transcription factor fusion protein, using dimeric FK506 or FK520 as the ligand and a promoter responsive to NF-AT or other transcription factor requiring two molecules for transcriptional activation.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
February 16, 1999
Assignees:
Board of Trustees of the Leland Stanford Junior University, President and Fellows of Harvard College
Inventors:
Gerald R. Crabtree, Stuart L. Schreiber, David M. Spencer, Thomas J. Wandless, Peter Belshaw, Steffan Ho