THE INTRACELLULAR-DISTRIBUTION AND PATTERN OF EXPRESSION OF MCL-1 OVERLAP WITH, BUT ARE NOT IDENTICAL TO, THOSE OF BCL-2

A family of genes related to the bcl-2 protooncogene has recently emerged. One member of this family, mel-1, was cloned from a human myeloblastic leukemia cell line (ML-1) undergoing differentiation. The intracellular localization of mel-1, as well as the kinetics of its expression during differentiation, have now been studied. These studies show that the intracellular distribution of mel-1 overlaps with, but is not identical to, that of bcl-2: mel-1 is similar to bcl-2 in that the mel-1 protein has a prominent mitochondrial localization, and in that it associates with membranes through its carboxyl hydrophobic tail. mcl-1 differs from bcl-2, however, in its relative distribution among other (nonmitochondrial/heavy membrane) compartments, mel-1 also being abundant in the light membrane fraction of immature ML-I cells while bcl-2 is abundant in the nuclear fraction. Similarly, in differentiating ML-1 cells, the timing of expression of mel-1 overlaps with, but is not identical to, that of bcl-2: the mel-1 protein increases rapidly as cells initiate differentiation, and mel-1 is a labile protein. In contrast, bcl-2 decreases gradually as cells complete differentiation. Overall, the mel-1 and bcl-2 proteins have some properties in common and others that are distinct. A burst of expression of mel-1, prominently associated with mitochondria, complements the continued expression of bcl-2 in ML-1 cells differentiating along the monocyte/macrophage pathway.