Inhibition of palmitoyl acyl transferase expression and/or activity for the regulation of antiproliferative factor activity
The invention generally concerns inhibition of a molecule that has a role in post-translational modification of a receptor for antiproliferative factor (APF) of bladder epithelial cells, thereby modulating the APF. In particular, inhibition of DHHC2 activity and/or ZDHHC2 expression results in modulation of APF receptor activity, and in specific aspects such modulation is therapeutic and/or preventative for a bladder condition, such as interstitial cystitis. In addition, inhibition of CKAP4 palmitoylation in certain cases also decreases its activity as a tPA receptor on smooth muscle cells or surfactant A on type II pneumocytes, and/or generally inhibits its function as a cell membrane receptor, cell chaperone molecule, and/or membrane trafficking agent.
1. A method of modulating activity of antiproliferative factor in an individual, comprising delivering to the individual a therapeutically effective amount of an agent that inhibits palmitoyl acyl transferase, wherein the palmitoyl acyl transferase is DHHC2.
2. The method of claim 1 , wherein the agent is a nucleic acid, protein, small molecule, or a mixture thereof.
3. The method of claim 1 , wherein the nucleic acid comprises siRNA.
4. The method of claim 1 , wherein the delivering step improves at least one symptom of a bladder condition.
5. The method of claim 4 , wherein the bladder condition is interstitial cystitis.
6. The method of claim 4 , wherein the individual is further provided an additional interstitial cystitis therapy.