CADP44 - A NOVEL REGULATORY SUBUNIT OF THE 26S PROTEASOME AND THE MAMMALIAN HOMOLOG OF YEAST SUG2P

We have identified a novel protein, CADp44, based on the analysis of c DNAs derived from the brainstem of the 13-lined ground squirrel, Sperm ophilus tridecemlineatus. CADp44 has an unmodified molecular mass of 4 4 178 Da and contains multiple functional domains, including a conserv ed ATPase domain (CAD) and a leucine zipper motif. We show that distin ct regions of the CADp44 sequence are identical to a set of peptides p repared from a recently identified bovine protein, referred to as p42, which is found in the PA700 regulatory complex of the 26S proteasome (DeMartino et al., 1996). We also show that CADp44 is the functional h omolog of the newly characterized Sug2 protein from the budding yeast, Saccharomyces cerevisiae (Russell et al., 1996). Consistent with its role as a component of the 26S proteasome, CADp44 mRNA is found in all ground squirrel tissues examined. Evolutionary relationships based on sequence analysis show that both CADp44 and yeast Sug2p are distinct from the other five CAD ATPases found in the PA700, and together compr ise the sixth and newest CAD subunit of the regulatory complex of the 26S proteasome.