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AssigneeThe Salk Institute for Biological Studies
InventorsKatherine A. Jones, Ping Wei, Mitchell Garber, Shi-Min Fang
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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.
An isolated Tat-associating polypeptide(s), or functional fragments thereof, wherein said polypeptide has a molecular weight of about 87 kDa and participates as a constituent of the TAK/TEFb complex, and wherein said polypeptide modulates Tat transactivation by enhancing the affinity if the Tat protein for TAR RNA.
An isolated Tat-associating polypeptide(s), or functional fragment thereof, wherein said polypeptide is encoded by a nucleotide sequence that hybridizes, under low stingency conditions, with a nucleotide sequence as set forth in nucleic acids 1-1440 of SEQ ID NO:1, and wherein said polypeptide modulates Tat transactivation by enhancing the affinity of the Tat protein for TAR RNA.
An isolated Tat-associating polypeptide, or functional fragments thereof, comprising an N-terminal cyclin box and a coiled-coil domain, wherein said polypeptide is present in a complex that is recongized by the transactivation domain of a Tat potein.
An isolated Tat-associating polypeptide, or functional fragment thereof, comprising an amino acid sequence containing a cyclin groove, an N-terminal cyclin box, and a coiled-coil domain, and wherein said polypeptide participates as a constituent of the TAK/TEFb complex and modulates Tat transactivation by enchancing the affinity of the Tat protein for TAR RNA.
An isolated human Tat-assocating polypeptide, or functional fragment thereof, comprising:
An isolated Tat-associating polypeptide containing an immunogenic epitope, wherein said polypeptide is encoded by nucleic acid that comprises a nucleotide sequence that hybridizes, under low stringency conditions, to nucleotides 1446-2103 as set forth in SEQ ID NO:1,
An epitope of a Tat-associating polypeptide, wherein nucleic acid encoding said epitope hybridizes, under low stringency conditions, to nucleotides 1446-2103 as set forth in SEQ ID NO:1.
Dependencies are inferred from the claim text.