Complex of a human foxc2 protein and a foxc2-interacting protein
AssigneeLeanGene AB
InventorsIsabel Climent-Johansson, Sven Enerback
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Abstract
The present invention relates to complexes of the FOXC2 protein with other proteins, in particular complexes of FOXC2 with proteins designated p621, NOLP, HSC71, FTP3, CLH1, and Kinase A Anchor Protein 84/149 (AKAP). The protein complexes can be used in methods of identifying agents useful for the treatment of medical conditions that can be treated by modulated FOXC2 activity, such as obesity, hypertriglyceridemia, diet-induced insulin resistance, and/or type 2 diabetes.
Claims23
A substantially pure protein complex comprising a first polypeptide and a second polypeptide, wherein the first polypeptide comprises the amino acid sequence of SEQ ID NO:1 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:2, 3, 4, 5, 6, or 7.
A method of modulating FOXC2 expression or activity, the method comprising contacting a cell expressing FOXC2 with an amount of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, 3, 4, 5, 6, or 7, or a nucleic acid encoding the polypeptide, sufficient to modulate the expression or activity of FOXC2 in the cell.
A method for the treatment or prophylaxis of a medical condition treatable by modulated FOXC2 activity, the method comprising administering to a patient in need of such treatment or prophylaxis an amount of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, 3, 4, 5, 6, or 7 effective to treat or prevent a medical condition treatable by modulated FOXC2 activity, and a pharmaceutically acceptable carrier.
A method of identifying an agent that modulates the formation of a FOXC2 protein complex, the method comprising:
- (i) contacting a first polypeptide comprising the amino acid sequence of SEQ ID NO:1 and a second polypeptide comprising the amino acid sequence of SEQ ID NO:2, 3, 4, 5, 6, or 7, in the presence of a candidate agent;
- (ii) measuring the formation of a complex between the first polypeptide and the second polypeptide in the presence of the candidate agent;
- and
- (iii) comparing the formation of the complex between the first polypeptide and the second polypeptide in the presence of the candidate agent with the formation of a complex between the first polypeptide and the second polypeptide in the absence of the candidate agent,
- to thereby determine whether the candidate agent modulates the formation of a FOXC2 protein complex.
A method of identifying an agent that modulates a FOXC2 activity, the method comprising:
- (i) contacting a first polypeptide comprising the amino acid sequence of SEQ ID NO:1 and a second polypeptide comprising the amino acid sequence of SEQ ID NO:2, 3, 4, 5, 6, or 7 in the presence of a candidate agent;
- (ii) measuring a FOXC2 activity of the first polypeptide in the presence of the candidate agent;
- and
- (iii) comparing the FOXC2 activity of the first polypeptide in the presence of the candidate agent with the FOXC2 activity of the first polypeptide in the absence of the candidate agent,
- to thereby determine whether the candidate agent modulates a FOXC2 activity.
A method of identifying an agent that modulates a FOXC2 activity, the method comprising:
- (i) contacting a first polypeptide comprising the amino acid sequence of SEQ ID NO:2, 3, 4, 5, 6, or 7 with a candidate agent;
- (ii) determining that the candidate agent binds to the first polypeptide;
- (iii) contacting a second polypeptide comprising the amino acid sequence of SEQ ID NO:1 with the candidate agent;
- (iv) measuring a FOXC2 activity of the second polypeptide in the presence of the candidate agent;
- and
- (v) comparing the FOXC2 activity of the second polypeptide in the presence of the candidate agent with the FOXC2 activity of the second polypeptide in the absence of the candidate agent,
- to thereby determine whether the candidate agent modulates a FOXC2 activity.
A method for purifying a FOXC2-interacting protein, the method comprising:
- (i) contacting a protein complex comprising a FOXC2 protein comprising the amino acid sequence of SEQ ID NO:1 and a FOXC2-interacting protein comprising the amino acid sequence of SEQ ID NO:2, 3, 4, 5, 6, or 7 with an antibody that binds to the protein complex;
- and
- (ii) purifying the FOXC2-interacting protein from the protein complex.
Dependencies are inferred from the claim text.