Targeting dimerization of BAX to modulate BAX activity
Methods are provided for identifying an agent that directly modulates a Bcl-2-associated x-protein (BAX) by promoting or disrupting dimerization of the BAX. Agents that directly modulate BAX by affecting dimerization are also provided.
1. A method of inhibiting BCL-2-associated X-protein (BAX) comprising contacting BAX with a peptide consisting of
a)
(SEQ ID NO: 12)
TWQTVTIFVAGVLTASLT,
b)
(SEQ ID NO: 13)
TWQTVTIFVAGVLTA, or
c)
(SEQ ID NO: 14)
TWQTVTIFVAGVL,
in an amount effective to inhibit BAX.
2. The method of claim 1 , wherein BAX is in a living cell and inhibition of BAX inhibits cell death.
3. The method of claim 1 , wherein the BAX is in a subject and the peptide is administered to the subject.
4. The method of claim 3 , wherein the subject is a human.
5. The method of claim 3 , wherein the subject has a disease or disorder associated with premature or unwanted cell death and characterized by abnormal activation, expression or function of BAX.
6. The method of claim 5 , wherein the disease or disorder is a cardiovascular disease or disorder, a neurodegenerative or neurological disease or disorder, a liver disease or disorder, a kidney disease or disorder, an immunological disorder, ischemia, infertility, a blood disorder, renal hypoxia, hepatitis, asthma or AIDS.
7. The method of claim 1 , wherein the peptide consists of the sequence TWQTVTIFVAGVLTASLT (SEQ ID NO:12).
8. The method of claim 1 , wherein the peptide consists of the sequence TWQTVTIFVAGVLTA (SEQ ID NO:13).
9. The method of claim 1 , wherein the peptide consists of the sequence TWQTVTIFVAGVL (SEQ ID NO:14).