A series of findings made by several researchers during a two-decade period between the mid-1950s and mid-1970s raised the suspicion that the lysosome might not be the organelle that degrades the bulk of cellular proteins Under basal conditions. These findings predicted the existence of a nonlysosomal, adenosine triphosphate (ATP)-dependent proteolytic system. Yet. following the initial discovery Of Such activity in a crude cell extract, it was a single article published in this Journal [A. Ciechanover, Y. Hod, A. Hershko, A heat-stable polypeptide component of in ATP-dependent proteolytic system from reticulocytes, Biochem. Biophys. Res. Common. 81 ( 1978) 1100-1105], my first Study as a graduate student of Avram Hershko, that made it clear that the system that catalyzes the activity is novel and complex. and (toes not follow the paradigm in the held of proteolysis where a single protease typically cleaves its Substrate: here at least two components were required to carry out this activity, and one of them was an unusual, small, and heat-stable protein later identified as ubiquitin. (C) 2009 Elsevier Inc, All rights reserved.