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Eukaryotic Cell, June 2009, p. 844-851, Vol. 8, No. 6
1535-9778/09/$08.00+0     doi:10.1128/EC.00165-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Characterization of a REG/PA28 Proteasome Activator Homolog in Dictyostelium discoideum Indicates that the Ubiquitin- and ATP-Independent REG{gamma} Proteasome Is an Ancient Nuclear Protease {triangledown} ,{dagger}

Patrick Masson,1 Daniel Lundin,2 Fredrik Söderbom,3 and Patrick Young4*

Swiss Institute of Bioinformatics, Swiss-Prot Group CMU, 1, rue Michel Servet, CH-1211 Geneva 4, Switzerland,1 Department of Molecular Biology and Functional Genomics, Stockholm University, S-10691 Stockholm, Sweden,2 Department of Molecular Biology, Swedish University of Agricultural Sciences (SLU), Uppsala Biomedical Center (BMC), Box 590, S-75124 Uppsala, Sweden,3 Department of Genetics Microbiology and Toxicology, Stockholm University, S-10691 Stockholm, Sweden4

Received 12 May 2008/ Accepted 10 April 2009

The nuclear proteasome activator REG{gamma}/PA28{gamma} is an ATP- and ubiquitin-independent activator of the 20S proteasome and has been proposed to degrade and thereby regulate both a key human oncogene, encoding the coactivator SRC-3/AIB1, and the cyclin-dependent kinase inhibitor p21 (Waf/Cip1). We report the identification and characterization of a PA28/REG homolog in Dictyostelium. Association of a recombinant Dictyostelium REG with the purified Dictyostelium 20S proteasome led to the preferential stimulation of the trypsin-like proteasome peptidase activity. Immunolocalization studies demonstrated that the proteasome activator is localized to the nucleus and is present in growing as well as starving Dictyostelium cells. Our results indicate that the Dictyostelium PA28/REG activator can stimulate both the trypsin-like and chymotrypsin-like activities of the 20S proteasome and supports the idea that the REG{gamma}-20S proteasome represents an early unique nuclear degradation pathway for eukaryotic cells.

* Corresponding author. Mailing address: Department of Genetics Microbiology and Toxicology, Stockholm University, S-10691 Stockholm, Sweden. Phone: 46-8-163107. Fax: 46-8-164315. E-mail: patrick.young{at}gmt.su.se

{triangledown} Published ahead of print on 1 May 2009.

{dagger} Supplemental material for this article may be found at http://ec.asm.org/.

Eukaryotic Cell, June 2009, p. 844-851, Vol. 8, No. 6
1535-9778/09/$08.00+0     doi:10.1128/EC.00165-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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