| 摘要 |
Shigella IpaB protein or functional derivative binds to interleukin-1 beta -converting enzyme (ICE) or an ICE homologue and activates a program of apoptosis. DNA encoding the Shigella IpaB protein, the IpaB protein or a functional derivative thereof is provided to a eukaryotic, preferably human, cell to induce apoptosis of that cell. This approach useful in treating diseases or disorders treatable by the eradication of unwanted cells, including cancer, autoimmunity, inflammation and chronic viral infections. Protein or peptide molecules (and the DNA coding therefor) which act as competitive antagonists for ICE binding without activating the apoptosis program are useful in treating or preventing diseases which involve an apoptotic mechanism in their pathogenesis, for example AIDS, degenerative diseases such as Alzheimer's disease, myelodysplastic disorders, ischemic injuries or toxin-induced liver diseases. Various methods of gene therapy relying upon controlled expression of IpaB in a target cell are disclosed. Also provided are methods for: inhibiting the interaction of an apoptosis-inducing protein or peptide with ICE, detecting a compound capable of inhibiting the binding of IpaB to ICE or to an ICE homologue, screening a candidate protein or peptide for its ability to interact with IpaB in a cell, isolating from a complex mixture a compound capable of binding to IpaB protein.
|
