The Salk Institute for Biological Studies

Katherine A Jones

Ping Wei

Shi-Min Fang

Mitchell Garber

Vanessa Bres

Lirong Zhang

Yupeng Chen

Provided herein are methods and compositions for modulating apoptosis by targeting SKIP (Ski-interacting protein) activity. Methods of increasing DNA damage-induced cell death in cancer cells, and reducing DNA damage-induced cell death in normal cells are provided.

Methods and compositions for targeting skip

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, formulations 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.

Transcriptional coactivator that interacts with Tat protein and regulates its binding to TAR RNA, methods for modulating Tat transactivation, and uses therefor

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, formulations 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.

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Encinitas, CA, United States of America

Katherine A Jones