The destruction of proteins in proteasomes is regulated at various levels. One of the early rate-limiting steps is 'tagging' of proteins with ubiquitin, an 8 kD molecule that, when present in chains of four residues or more, serves as a signal recognized by proteasomal subunits. Ubiquitin is attached to target proteins by a series of enzymatic steps involving an El (ubiquitin activating enzyme), E2 (ubiquitin conjugating enzyme), and E3 (ubiquitin protein ligase). It is the last enzyme that confers target protein specificity. We have found that members of a family of RING domain containing proteins with anti- apoptotic activity, IAPs,
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