MUC1, caspase-8, and DED-containing proteins
The disclosure features a variety of compositions and methods for modulating an interaction between MUC1 and caspase-8 and/or an interaction between MUC1 and a DED-containing protein (e.g., an anti-apoptotic DED-containing protein or a pro-apoptotic DED-containing protein). Such methods and compositions are useful for the treatment or prevention of e.g., a variety of pathological disorders characterized by elevated or decreased levels of apoptosis. Moreover, the compositions and methods are also useful to identify, design, and generate compounds that modulate the interactions. The compounds and/or pharmaceutical compositions containing the compounds can be used in the treatment of disease.
1. A method of identifying a compound that modulates the binding of MUC1 to caspase-8, the method comprising:
contacting a MUC1 reagent with a caspase-8 reagent or a DED-containing protein reagent in the presence of a candidate compound; and
determining whether the candidate compound modulates binding of the MUC1 reagent to the caspase-8 reagent.
2. The method of claim 1 , wherein the DED-containing protein reagent comprises FADD or a DED-containing fragment thereof.
3. The method of claim 1 , wherein the caspase-8 reagent comprises a full-length, unprocessed caspase-8.
4. The method of claim 3 , wherein the full-length unprocessed caspase-8 comprises SEQ ID NO:5.
5. The method of claim 1 , wherein the MUC1 reagent comprises the cytoplasmic domain of MUC1.
6. The method of claim 5 , wherein the cytoplasmic domain of MUC1 comprises SEQ ID NO: 2.
7. The method of claim 1 , wherein the MUC1 reagent comprises SEQ ID NO:3.
8. The method of claim 1 , wherein the modulation is inhibition.
9. The method of claim 1 , wherein the modulation is enhancement.
10. The method of claim 1 , wherein the contacting occurs in a cell.