After HIV has settled into a chromosome, a viral protein called Tat (transactivating tranxion factor) accelerates the production of new virus particles. Without Tat, an infection would not be likely to get off the ground. Researchers have known that Tat does not function alone, but requires help from a partner molecule in the cell. However, the nature of the cellular partner remained elusive. This invention covers the discovery of the molecule called cyclin T which appears to be Tat’s partner. This discovery opens the door to developing a new class of therapeutic agents for AIDS based on blocking the chain of events created by the Tat-Cyclin T connection.
References
Genes & Development 11: 2593-2599 (1997)
Cell 92: 451-462 (1998)
Genes & Development 12: 3512-3527 (1998)
Mol. Cell. Biol. 20: 6958-6969 (2000)
J. Biol. Chem. 275: 34314-34319 (2000)
Patent Status:
U.S. Patent No. 6,270,956 issued August 7, 2001
U.S. Patent No. 6,284,456 issued September 4, 2001
“The patents are owned and controlled by the Salk Institute and a license from the Institute would be required to use the technology covered in the patents.”
“Perhaps Mr. Fang does not understand that as an employee of Salk, he was required to assign his rights to the Salk Institute per his employment agreement and Salk’s patent policy.”
Translational coactivator that interacts with Tat protein and regulates its binding to TAR RNA, methods for modulating Tat transactivation, and uses therefor
Abstract
In accordance with the present invention, a host cell protein has been discovered which regulates Tat transactivation. The protein is the first discovered constituent of the TAK/TEFb complex which associates with the HIV Tat, via divalent cation metals, and is necessary for the binding of Tat to TAR RNA. This protein, cyclin T1, is an 87 kDa cyclin partner for the PITALRE kinase. It is further discovered that Tat must interact with TAK in order to bind to TAR RNA with affinity and with the appropriate sequence specificity that is observed in vivo. In accordance with another aspect of the invention, xulations useful for modulation of Tat transactivation have been developed. In addition, assays have been developed for the identification of compounds useful to modulate the above-described processes.
Inventors: Jones; Katherine A. (Encinitas, CA), Wei; Ping (Brookeville, MD), Garber; Mitchell (Woodland Hills, CA), Fang; Shi-Min (San Diego, CA)
Assignee: The Salk Institute for Biological Studies (La Jolla, CA)
Appl. No.: 09/126,980
Filed: July 30, 1998
United States Patent 6,284,456
Jones , et al. September 4, 2001
Tranxional coactivator that interacts with Tat protein and regulates its binding to TAR RNA, methods for modulating Tat transactivation, and uses therefor
Abstract
In accordance with the present invention, isolated nucleic acid encoding a host cell protein that regulates Tat transactivation has been discovered. The protein is the first discovered constituent of the TAK/TEFb complex which associates with the HIV Tat, via divalent cation metals, and is necessary for the binding of Tat to TAR RNA. This protein, cyclin T1, is an 87 kDa cyclin partner for the PITALRE kinase. It is further discovered that Tat must interact with TAK in order to bind to TAR RNA with affinity and with the appropriate sequence specificity that is observed in vivo. In accordance with another aspect of the invention, xulations useful for modulation of Tat transactivation have been developed. In addition, assays have been developed for the identification of compounds useful to modulate the above-described processes.
Inventors: Jones; Katherine A. (Encinitas, CA), Wei; Ping (San Diego, CA), Garber; Mitchell (Woodland Hills, CA), Fang; Shi-Min (San Diego, CA)
Assignee: The Salk Institute for Biological Studies (La Jolla, CA)