Regulated apoptosis
We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins and disclose methods and materials for using that procedure to regulatably initiate cell-specific apoptosis (programmed cell death) in genetically engineered cells.
1. A nucleic acid construct encoding a chimeric protein comprising
three consecutive FKBP12 domains and
a heterologous protein domain comprising the cytoplasmic signaling domain of Fas.
2. A chimeric protein encoded by the nucleic acid construct of claim 1 .
3. A nucleic acid construct encoding a chimeric protein comprising
three consecutive cyclophilin domains and
a heterologous protein domain comprising the cytoplasmic signaling domain of Fas.
4. A nucleic acid construct encoding a chimeric protein comprising
four consecutive cyclophilin domains and
a heterologous protein domain comprising the cytoplasmic signaling domain of Fas.
5. A chimeric protein encoded by the nucleic acid construct of claim 3 .
6. A chimeric protein encoded by the nucleic acid construct of claim 4 .
7. A vector comprising the nucleic acid construct of claim 1 .
8. A vector comprising the nucleic acid construct of claim 3 .
9. The vector of claim 7 , wherein said vector is a viral vector.
10. An isolated mammalian cell containing and capable of expressing the nucleic acid construct of claim 3 .