Proteasome subunit Rpn13 is a novel ubiquitin receptor

Proteasomal receptors that recognize ubiquitin chains attached to substrates are key mediators of selective protein degradation in eukaryotes. Here we report the identification of a new ubiquitin receptor, Rpn13/ARM1, a known component of the proteasome. Rpn13 binds ubiquitin through a conserved amino-terminal region termed the pleckstrin-like receptor for ubiquitin (Pru) domain, which binds K48-linked diubiquitin with an affinity of approximately 90 nM. Like proteasomal ubiquitin receptor Rpn10/S5a, Rpn13 also binds ubiquitin-like (UBL) domains of UBL-ubiquitin-associated (UBA) proteins. In yeast, a synthetic phenotype results when specific mutations of the ubiquitin binding sites of Rpn10 and Rpn13 are combined, indicating functional linkage between these ubiquitin receptors. Because Rpn13 is also the proteasomal receptor for Uch37, a deubiquitinating enzyme, our findings suggest a coupling of chain recognition and disassembly at the proteasome.

[1]  P. Howley,et al.  The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome. , 2000, Molecular cell.

[2]  H. Yokosawa,et al.  Ubiquitin-like proteins and Rpn10 play cooperative roles in ubiquitin-dependent proteolysis. , 2002, Biochemical and biophysical research communications.

[3]  D. Koepp,et al.  Ubiquitin receptor proteins hHR23a and hPLIC2 interact. , 2007, Journal of molecular biology.

[4]  Je-Hyun Baek,et al.  Rpn13p and Rpn14p are involved in the recognition of ubiquitinated Gcn4p by the 26S proteasome , 2007, FEBS letters.

[5]  J. Yates,et al.  Proteasomal proteomics: identification of nucleotide-sensitive proteasome-interacting proteins by mass spectrometric analysis of affinity-purified proteasomes. , 2000, Molecular biology of the cell.

[6]  I. Dikic,et al.  erratum: Cbl–CIN85–endophilin complex mediates ligand-induced downregulation of EGF receptors , 2002, Nature.

[7]  D. Finley,et al.  Rad23 and Rpn10 Serve as Alternative Ubiquitin Receptors for the Proteasome* , 2004, Journal of Biological Chemistry.

[8]  Tohru Natsume,et al.  A novel proteasome interacting protein recruits the deubiquitinating enzyme UCH37 to 26S proteasomes , 2006, The EMBO journal.

[9]  A. Varshavsky,et al.  Ubiquitin as a degradation signal. , 1992, The EMBO journal.

[10]  R. Deshaies,et al.  Multiubiquitin Chain Receptors Define a Layer of Substrate Selectivity in the Ubiquitin-Proteasome System , 2004, Cell.

[11]  P. Howley,et al.  Ubiquitin recognition by the DNA repair protein hHR23a. , 2003, Biochemistry.

[12]  Anna Bakhrat,et al.  The DNA Damage-Inducible UbL-UbA Protein Ddi1 Participates in Mec1-Mediated Degradation of Ho Endonuclease , 2005, Molecular and Cellular Biology.

[13]  C. Pickart,et al.  Binding of polyubiquitin chains to ubiquitin-associated (UBA) domains of HHR23A. , 2004, Journal of molecular biology.

[14]  G. Dittmar,et al.  Proteasome subunit Rpn1 binds ubiquitin-like protein domains , 2002, Nature Cell Biology.

[15]  M. Glickman,et al.  Complementary Roles for Rpn11 and Ubp6 in Deubiquitination and Proteolysis by the Proteasome* , 2004, Journal of Biological Chemistry.

[16]  C. Pickart,et al.  Rad23 Ubiquitin-associated Domains (UBA) Inhibit 26 S Proteasome-catalyzed Proteolysis by Sequestering Lysine 48-linked Polyubiquitin Chains* , 2003, The Journal of Biological Chemistry.

[17]  A. Goldberg,et al.  hRpn13/ADRM1/GP110 is a novel proteasome subunit that binds the deubiquitinating enzyme, UCH37 , 2006, The EMBO journal.

[18]  Ivan Dikic,et al.  Ubiquitin docking at the proteasome through a novel pleckstrin-homology domain interaction , 2008, Nature.

[19]  M. Washburn,et al.  Proteasome recruitment and activation of the Uch37 deubiquitinating enzyme by Adrm1 , 2006, Nature Cell Biology.

[20]  S. Elsasser,et al.  Delivery of ubiquitinated substrates to protein-unfolding machines , 2005, Nature Cell Biology.

[21]  K. N. Chandrika,et al.  Analysis of the human protein interactome and comparison with yeast, worm and fly interaction datasets , 2006, Nature Genetics.

[22]  Gerhard Wagner,et al.  Structural studies of the interaction between ubiquitin family proteins and proteasome subunit S5a. , 2002, Biochemistry.

[23]  Li Chen,et al.  Rad23 Promotes the Targeting of Proteolytic Substrates to the Proteasome , 2002, Molecular and Cellular Biology.

[24]  H. Ploegh,et al.  Multiple associated proteins regulate proteasome structure and function. , 2002, Molecular cell.

[25]  T. Rando,et al.  Regulation of Pax3 by Proteasomal Degradation of Monoubiquitinated Protein in Skeletal Muscle Progenitors , 2007, Cell.

[26]  W. Baumeister,et al.  The 26S proteasome: a molecular machine designed for controlled proteolysis. , 1999, Annual review of biochemistry.

[27]  H. Yokosawa,et al.  Sem1p Is a Novel Subunit of the 26 S Proteasome from Saccharomyces cerevisiae* , 2004, Journal of Biological Chemistry.

[28]  J. Hoeijmakers,et al.  Interaction of hHR23 with S5a , 1999, Journal of Biological Chemistry.

[29]  W. Baumeister,et al.  A Subcomplex of the Proteasome Regulatory Particle Required for Ubiquitin-Conjugate Degradation and Related to the COP9-Signalosome and eIF3 , 1998, Cell.

[30]  R. Hartmann-Petersen,et al.  Adrm1, a putative cell adhesion regulating protein, is a novel proteasome-associated factor. , 2006, Journal of molecular biology.

[31]  Q. Deveraux,et al.  A 26 S protease subunit that binds ubiquitin conjugates. , 1994, The Journal of biological chemistry.

[32]  D. Finley,et al.  Proteasome-associated proteins: regulation of a proteolytic machine , 2005, Biological chemistry.

[33]  Colin Gordon,et al.  Proteins containing the UBA domain are able to bind to multi-ubiquitin chains , 2001, Nature Cell Biology.

[34]  G. Wider,et al.  Ubiquitin-Binding Domains in Y-Family Polymerases Regulate Translesion Synthesis , 2005, Science.

[35]  Wei Xu,et al.  Editing of ubiquitin conjugates by an isopeptidase in the 26S proteasome , 1997, Nature.

[36]  R. Ozawa,et al.  A comprehensive two-hybrid analysis to explore the yeast protein interactome , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[37]  D. J. Clarke,et al.  UBA domains of DNA damage-inducible proteins interact with ubiquitin , 2001, Nature Structural Biology.

[38]  K. Madura.  Rad23 and Rpn10: perennial wallflowers join the melee. , 2004, Trends in biochemical sciences.