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US 6,720,181 B1Granted
Ubiquitin ligases as therapeutic targets
AssigneeNew York University
InventorsDah Shiarn Chiaur, Michele Pagano, Esther Latres
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AssigneeNew York University
InventorsDah Shiarn Chiaur, Michele Pagano, Esther Latres
Estimating the term…
The present invention relates to the discovery, identification and characterization of nucleotides that encode novel substrate-targeting subunits of ubiquitin ligases. The invention encompasses nucleotides encoding novel substrate-targeting subunits of ubiquitin ligases: FBP1, FBP2, FBP3, FBP4, FBP5, FBP6, FBP7, FBP8, FBP9, FBP10, FBP11, FBP12, FBP13, FBP14, FBP15, FBP16, FBP17, FBP18, FBP19, FBP20, FBP21, FBP22, FBP23, FBP24, and FBP25, transgenic mice, knock-out mice, host cell expression systems and proteins encoded by the nucleotides of the present invention. The present invention relates to screening assays that use the novel substrate-targeting subunits to identify potential therapeutic agents such as small molecules, compounds or derivatives and analogues of the novel ubiquitin ligases which modulate activity of the novel ubiquitin ligases for the treatment of proliferative and differentiative disorders, such as cancer, major opportunistic infections, immune disorders, certain cardiovascular diseases, and inflammatory disorders. The invention further encompasses therapeutic protocols and pharmaceutical compositions designed to target ubiquitin ligases and their substrates for the treatment of proliferative disorders.
An isolated nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:5.
An isolated nucleic acid molecule comprising a nucleotide sequence which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:6.
An isolated nucleic acid molecule comprising a contiguous open reading frame which encodes a polypeptide which 1) binds to Skp1 and 2) comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:6 over the entire length of SEQ ID NO:6, or a complement of a coding or non-coding strand thereof, wherein said polypeptide has ubiquitination activity.
An isolated nucleic acid molecule comprising a nucleotide sequence which 1) encodes a polypeptide which binds to Skp1, and 2) hybridizes contiguously over its full length to a second nucleic acid molecule consisting of the nucleotide sequence of SEQ ID NO:5, under conditions of incubation at 65° C. in 0.5 M NaHPO4, 7% sodium dodecyl sulfate (SDS), 1 mM EDTA followed by washing in 0.1×SSC/0.1% SDS at 65° C., wherein said polypeptide has ubiquitination activity, and has at least 95% sequence identity to SEQ ID NO:6.
A method for detecting the presence of a nucleic acid molecule comprising the contiguous nucleotide sequence of SEQ ID NO:5 in a sample, said method comprising the steps of:
An isolated nucleic acid molecule comprising a nucleotide sequence which encodes a fusion polypeptide comprising a contiguous amino acid sequence encoded by the nucleotide sequence of SEQ ID NO:5.
Dependencies are inferred from the claim text.