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US 2002/0173026 A1Published application
Survivin-interacting proteins and use thereof
AssigneeMyriad Genetics, Inc.
InventorsDaniel Albert Wettstein, Daniel Cimbora
Life of this patent
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Abstract
Protein complexes are provided comprising survivin and one or more proteins selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT. The protein complexes are useful in screening assays for identifying compounds effective in modulating the protein complexes and in treating and/or preventing diseases and disorders associated with survivin and its interacting partner proteins. In addition, methods of detecting the protein complexes and modulating the functions and activities of the protein complexes or interacting members thereof are also provided.
Claims38
An isolated protein complex having a first protein which is survivin or a homologue or derivative or fragment thereof interacting with a second protein which is a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT or a homologue or derivative or fragment thereof.
An isolated protein complex comprising a first protein interacting with a second protein, wherein:
- (a) said first protein is selected from the group consisting of
- (i) survivin,
- (ii) a survivin fragment capable of interacting with a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT, and
- (iii) a fusion protein containing survivin or said survivin fragment;
- and
- (b) said second protein is selected from the group consisting of
- (1) a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT,
- (2) a fragment of a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT and capable of interacting with survivin, and
- (3) a fusion protein containing a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT or said fragment.
6 more elements
A fusion protein having a first polypeptide covalently linked to a second polypeptide, wherein said first polypeptide is survivin or a homologue or fragment thereof, and wherein said second polypeptide is a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT or a homologue or fragment thereof.
A method for selecting modulators of an interaction between a first protein and a second protein,
- (a) said first protein being selected from the group consisting of
- (i) survivin,
- (ii) a survivin homologue having an amino acid sequence at least 90% identical to that of survivin and capable of interacting with a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT,
- (iii) a survivin fragment capable of interacting with a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT, and
- (iv) a fusion protein containing survivin, said survivin homologue or said survivin fragment;
- and
- (b) said second protein being selected from the group consisting of
- (1) HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT,
- (2) a homologue of a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT having an amino acid sequence at least 90% identical to that of said protein and capable of interacting with survivin,
- (3) a fragment of a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT and capable of interacting with survivin, and
- (4) a fusion protein containing a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT, said protein homologue or said protein fragment, said method comprising:
- contacting said first protein with said second protein in the presence of a test compound;
- and
- detecting the interaction between said first protein and said second protein.
11 more elements
A method for selecting modulators of an interaction between a first polypeptide and a second polypeptide, said first polypeptide being survivin or a homologue or fragment thereof and said second polypeptide being a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT or a homologue or fragment thereof, said method comprising:
- providing in a host cell a first fusion protein having said first polypeptide, and a second fusion protein having said second polypeptide, wherein a DNA binding domain is fused to one of said first and second polypeptides while a transcription-activating domain is fused to the other of said first and second polypeptides;
- providing in said host cell a reporter gene, wherein the transcription of the reporter gene is controlled by the interaction between the first polypeptide and the second polypeptide;
- allowing said first and second fusion proteins to interact with each other within said host cell in the presence of a test compound;
- and
- determining the expression of said reporter gene.
2 more elements
A method for selecting compounds capable of interfering with the interaction between a first protein and a second protein, wherein
- (a) said first protein is selected from the group consisting of
- (i) survivin,
- (ii) a survivin homologue having an amino acid sequence at least 90% identical to that of survivin and capable of interacting with a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT,
- (iii) a survivin fragment capable of interacting with a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT, and
- (iv) a fusion protein containing survivin, said survivin homologue or said survivin fragment;
- and
- (b) said second protein is selected from the group consisting of
- (1) HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT,
- (2) a homologue of a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT having an amino acid sequence at least 90% identical to that of said protein and capable of interacting with survivin,
- (3) a fragment of a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT capable of interacting with survivin, and
- (4) a fusion protein containing a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT, said protein homologue or said protein fragment, said method comprising:
- contacting said first protein with said second protein in the presence of a test compound and detecting the interaction between said first protein and said second protein;
- and
- contacting said first protein with said second protein in the absence of said test compound and detecting the interaction between said first protein and said second protein.
11 more elements
A composition comprising:
- a first expression vector having a nucleic acid encoding a first protein;
- and
- a second expression vector having a nucleic acid encoding a second protein, wherein:
- (a) said first protein is selected from the group consisting of
- (i) survivin,
- (ii) a survivin homologue having an amino acid sequence at least 90% identical to that of survivin and capable of interacting with a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT,
- (iii) a survivin fragment capable of interacting with a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT, and
- (iv) a fusion protein containing survivin, said survivin homologue or said survivin fragment;
- and
- (b) said second protein is selected from the group consisting of
- (1) HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT,
- (2) a homologue of a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT having an amino acid sequence at least 90% identical to that of said protein and capable of interacting with survivin,
- (3) a fragment of a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT capable of interacting with survivin, and
- (4) a fusion protein containing a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT, said protein homologue or said protein fragment.
11 more elements
An expression vector comprising:
- (a) a first nucleic acid encoding a first protein selected from the group consisting of
- (i) survivin,
- (ii) a survivin homologue having an amino acid sequence at least 90% identical to that of survivin and capable of interacting with a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT,
- (iii) a survivin fragment capable of interacting with a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT, and
- (iv) a fusion protein containing survivin, said survivin homologue or said survivin fragment;
- and
- (b) a second nucleic acid encoding a second protein selected from the group consisting of
- (1) HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT,
- (2) a homologue of a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT having an amino acid sequence at least 90% identical to that of said protein and capable of interacting with survivin,
- (3) a fragment of a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT and capable of interacting with survivin, and
- (4) a fusion protein containing a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT, said protein homologue or said protein fragment.
8 more elements
A host cell comprising:
- a first expression vector having a nucleic acid encoding a first protein;
- and
- a second expression vector having a nucleic acid encoding a second protein, wherein:
- (a) said first protein is selected from the group consisting of
- (i) survivin,
- (ii) a survivin homologue having an amino acid sequence at least 90% identical to that of survivin and capable of interacting with a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT,
- (iii) a survivin fragment capable of interacting with a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT, and
- (iv) a fusion protein containing survivin, said survivin homologue or said survivin fragment;
- and
- (b) said second protein is selected from the group consisting of
- (1) HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT,
- (2) a homologue of a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT and having an amino acid sequence at least 90% identical to that of said protein and capable of interacting with survivin,
- (3) a fragment of a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT and capable of interacting with survivin, and
- (4) a fusion protein containing a protein selected from the group consisting of HDLC1, beta-actin, DNA helicase II, COPP, OSTP, SLC8A1, A2-CAT, said protein homologue or said protein fragment.
11 more elements
Dependencies are inferred from the claim text.