Inhibiting apoptosis with adenovirus RID protein

DETAILED DESCRIPTION In accordance with the present invention, the inventor herein has succeeded in discovering that the Ad 10.
4K/14.
5K complex inhibits apoptosis mediated by death receptors, in particular Fas or TNFR-1, by removing the death receptor from the cell surface.
The present invention, thus, provides a method for inhibiting apoptosis of a cell comprising treating the cell with an effective amount of a 10.
4K/14.
5K complex referenced herein as RID (Receptor Internalization and Death) or as RID complex.
The RID complex reduces the number of molecules of one or more death receptors on the surface of the cell.
This down-regulation of the death receptor results from internalization of the receptor to endosomes and degradation of the internalized death receptor by lysozymes.
The RID complex is obtained from or derived from the RID.
alpha.
and RID.
beta.
proteins encoded by the Ad E3 region DNA.
Other E3 region-encoded proteins, including the gp19K and 14.
7K proteins, are not required to remove the death receptor from the cell surface or to induce apoptosis.
Due to the similar structure of TNFR death receptors, and in the common pathway by which they mediate apoptosis, it is believed that RID can inhibit apoptosis mediated by all death receptor members of the TNFR family by promoting their removal from the cell surface.
In one embodiment of the present invention, the cell is treated with RID by administering to the cell a polynucleotide encoding the RID complex, through which the RID complex is expressed in the cell.
Alternatively, the treating step comprises administering the RID complex to the cell, preferably in a carrier that facilitates delivery of the complex into the cell.
The method can be used to inhibit apoptosis of cells expressing one or more death receptors of the TNFR family, including but not limited to Fas, TNFR-1, DR3, TRAIL-R1 and TRAIL-R2.
Where the cell comprises a tissue, the method is useful for promoting survival of a tissue transplant in a patient or in promoting survival of a tissue under attack in a patient suffering from a degenerative disease, an immunodeficiency disease, an autoimmune disorder or other diseases associated with disregulation of apoptosis mediated by the TNFR death receptors