Induced expression of a ubiquitin COOH-terminal hydrolase in acute lymphoblastic leukemia.

To identify potential effector molecules of human B-cell differentiation, the acute lymphoblastic leukemia cells (Reh) were induced to terminal differentiation in vitro using the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate. Proteins of parent and differentiated Reh cells were mapped using powerful two-dimensional gel electrophoresis coupled with ultrasensitive silver stain. New protein (MW-pl; p34-5.3) spot was induced in the differentiated Reh cells. The NH2-terminal sequencing of this protein revealed 100% homology with the ubiquitin COOH-terminal hydrolase isozyme L1 (UCH-L1). The presence of UCH-L1 protein in the differentiated Reh cells but not in parent cells was confirmed by immunocytochemistry and Western blot. The cDNA for this enzyme was cloned from the differentiated Reh cells, and the UCH-L1 mRNA was detected in both parent and 12-O-tetradecanoylphorbol-13-acetate-induced cells. However, the message was more abundant in the differentiated cells than parent cells, indicating a posttranscriptional regulation. Until now, UCH-L1 was thought to be neuron-specific. The induced expression of UCH-L1 in differentiated Reh cells argues for a role of this enzyme, and the ubiquitin system, in B-cell differentiation.