Abstract: The present invention provides methods to identify ISG15 target proteins, methods to identify compounds that alter the conjugation of ISG15 with target proteins, methods for altering the level of ISG15-conjugated protein in a patient or a sample, methods to diagnose a patient having a malcondition characterized by an altered level of ISG15-conjugated protein, ISG15-conjugates, methods to treat cancer by promoting conjugation of a target protein to ISG15, and antibodies that selectively bind to ISG15-conjugates.

Abstract: The present invention is directed to identification of agents that modulate UBP43 activity as well as associated methods, uses, processes, compositions and agents. In particular, the invention is directed to in vivo and in vitro methods to identify an agent that inhibits or stimulates UBP43 activity within a cell, a method for inducing cellular apoptosis, a method for affecting cellular reaction to interferon, a method for treating disease associated with cellular proliferation by causing apoptosis, and a method for treating both acute and chronic diseases in which interferon exerts a beneficial effect. The invention is also directed to modified ISG15-conjugates that have lowered or no susceptibility to UBP43 cleavage, pharmaceutical compositions of the agents, conjugates, and additional modified ISG15-conjugates.