IDENTIFICATION OF A PHYLOGENETICALLY CONSERVED SUG1 CAD FAMILY MEMBERTHAT IS DIFFERENTIALLY EXPRESSED IN THE MOUSE NERVOUS-SYSTEM

We have isolated a cDNA clone from mouse, m56, that encodes a member o f the Conserved ATPase-containing Domain (CAD) protein family. Sequenc e analysis revealed that m56 is identical to mouse mSug1/FZA-B and sha res high homology with human Trip1, moth 18-56, and yeast Sug1. When e xamined, Sug1-like CAD proteins appear to function in the regulation o f the 26S proteasome, as well as associate with members of the steroid /thyroid receptor superfamily and other transcriptional activators. m5 6 can complement the lethal phenotype of loss of SUG1 in yeast. We hav e examined the tissue distribution of m56 using Northern and Western b lots, in addition to immunocytochemistry and in situ hybridization. Wh ile m56 was expressed in all tissues and cells examined, several class es of neurons, most notably in the hippocampus, olfactory bulb, and ce rebellum, displayed elevated levels of m56 mRNA and protein. We also e xamined distribution of RNA polymerase II and 26S proteasome subunit 4 (S4) within the mouse brain by in situ hybridization. While all three genes had similar patterns of expression, there were significant diff erences among them. In moths, the expression of the Sug1 homolog 18-56 is dramatically up-regulated during programmed cell death. In additio n, it has been previously demonstrated that the proteasome plays an es sential role in the regulation of apoptosis in mammals. We examined th e expression of m56 in mouse during natural and induced cell death in a variety of tissues and found no significant changes in expression. T aken together, the data presented here suggest that while m56 is a hig hly conserved gene that presumably plays essential but complex roles i n basal and developmental processes, it may not represent a rate-limit ing step in these processes. (C) 1997 John Wiley & Sons, Inc.