A Proteasome Activator Subunit Binds Calcium (*)
- From the Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah 84132
Abstract
We recently cloned a cDNA encoding the 29-kDa subunit of human red blood cell regulator (REG), a potent activator of the multicatalytic
protease (Realini, C., Dubiel, W., Pratt, G., Ferrell, K., and Rechsteiner, M.(1994) J. Biol. Chem. 269, 20727-20732). The sequence of this subunit contains 28 “alternating” lysine and glutamic acid residues (a KEKE motif).
Similar regions are present in a number of Ca
-binding proteins, and using standard filter assays, the recombinant protein is shown to bind 
Ca
and ruthenium red. 
Ca
is also bound to a ubiquitin extension protein containing the 28-residue KEKE region from the 29-kDa REG subunit. Thus, the
29-kDa REG subunit is a Ca
-binding protein, and its KEKE region is able to bind divalent cations. Ca
reversibly inhibits the enhanced peptidase activity of complexes between the multicatalytic protease and recombinant REG.
This raises the possibility that multicatalytic protease activity is regulated by calcium in vivo.
Footnotes
-
↵* These studies were supported by National Institutes of Health Grant GM37009 and by a grant from the Lucille P. Markey Charitable Trust. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The abbreviations used are:
- MCP
-
multicatalytic protease
- KEKE
-
alternating lysine (K) and glutamate (E) amino acids
- rREG
-
recombinant 29-kDa subunit of 11 S regulator
- MCA
-
7-amino-4-methylcoumarin
- sLLVY
-
succinyl-Leu-Leu-Val-Tyr
- Ub
-
ubiquitin.
-
↵2W. Dubiel, unpublished observation.
-
↵3Z. Zhang, C. Realini, and M. Rechsteiner, manuscript in preparation.
-
↵4C. Realini, unpublished observation.
-
- Received September 12, 1995.
- Revision received October 20, 1995.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
