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PMID: 17646385 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Rpn10-mediated degradation of ubiquitinated proteins is essential for mouse development.

Molecular and cellular biology ·Vol. 27 ·No. 19 ·2007-10-00 ·Pages 6629-38

Hamazaki J, Sasaki K, Kawahara H, Hisanaga S, Tanaka K, Murata S

Abstract

Rpn10 is a subunit of the 26S proteasome that recognizes polyubiquitinated proteins. The importance of Rpn10 in ubiquitin-mediated proteolysis is debatable, since a deficiency of Rpn10 causes different phenotypes in different organisms. To date, the role of mammalian Rpn10 has not been examined genetically. Moreover, vertebrates have five splice variants of Rpn10 whose expressions are developmentally regulated, but their biological significance is not understood. To address these issues, we generated three kinds of Rpn10 mutant mice. Rpn10 knockout resulted in early-embryonic lethality, demonstrating the essential role of Rpn10 in mouse development. Rpn10a knock-in mice, which exclusively expressed the constitutive type of Rpn10 and did not express vertebrate-specific variants, grew normally, indicating that Rpn10 diversity is not essential for conventional development. Mice expressing the N-terminal portion of Rpn10, which contained a von Willebrand factor A (VWA) domain but lacked ubiquitin-interacting motifs (Rpn10DeltaUIM), also exhibited embryonic lethality, suggesting the important contribution of UIM domains to viability, but survived longer than Rpn10-null mice, consistent with a "facilitator" function of the VWA domain. Biochemical analysis of the Rpn10DeltaUIM liver showed specific impairment of degradation of ubiquitinated proteins. Our results demonstrate that Rpn10-mediated degradation of ubiquitinated proteins, catalyzed by UIMs, is indispensable for mammalian life.

MeSH Terms
Alternative Splicing Animals Carrier Proteins/genetics,metabolism Embryo, Mammalian/anatomy & histology,physiology Gene Targeting Liver/metabolism Mice/embryology,growth & development,metabolism Mice, Knockout Polyubiquitin/metabolism Proteasome Endopeptidase Complex/chemistry,genetics,metabolism Protein Subunits/genetics,metabolism RNA-Binding Proteins Ubiquitination
Chemicals
Carrier Proteins Protein Subunits Psmd4 protein, mouse RNA-Binding Proteins Polyubiquitin Proteasome Endopeptidase Complex ATP dependent 26S protease
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Hamazaki Jun
Laboratory of Frontier Science, Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Sasaki Katsuhiro
Kawahara Hiroyuki
Hisanaga Shin-Ichi
Tanaka Keiji
Murata Shigeo
References (50)
50 references, click to expand
  1. Growth retardation in mice lacking the proteasome activator PA28gamma.
    J Biol Chem. 1999 Dec 31;274(53):38211-5 PMID: 10608895
  2. The ubiquitin system.
    Annu Rev Biochem. 1998;67:425-79 PMID: 9759494
  3. Mouse proteasomal ATPases Psmc3 and Psmc4: genomic organization and gene targeting.
    Genomics. 2000 Jul 1;67(1):1-7 PMID: 10945464
  4. RPN4 is a ligand, substrate, and transcriptional regulator of the 26S proteasome: a negative feedback circuit.
    Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3056-61 PMID: 11248031
  5. UBA domains of DNA damage-inducible proteins interact with ubiquitin.
    Nat Struct Biol. 2001 May;8(5):417-22 PMID: 11323716
  6. Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knock-outs using Cre recombinase.
    J Biol Chem. 1999 Jan 1;274(1):305-15 PMID: 9867845
  7. Multiubiquitin chain binding subunit MCB1 (RPN10) of the 26S proteasome is essential for developmental progression in Physcomitrella patens.
    Plant Cell. 1999 Aug;11(8):1457-72 PMID: 10449580
  8. Pleiotropic defects caused by loss of the proteasome-interacting factors Rad23 and Rpn10 of Saccharomyces cerevisiae.
    Genetics. 1999 Sep;153(1):69-79 PMID: 10471701
  9. Interaction of hHR23 with S5a. The ubiquitin-like domain of hHR23 mediates interaction with S5a subunit of 26 S proteasome.
    J Biol Chem. 1999 Sep 24;274(39):28019-25 PMID: 10488153
  10. A series of ubiquitin binding factors connects CDC48/p97 to substrate multiubiquitylation and proteasomal targeting.
    Cell. 2005 Jan 14;120(1):73-84 PMID: 15652483
  11. A heterodimeric complex that promotes the assembly of mammalian 20S proteasomes.
    Nature. 2005 Oct 27;437(7063):1381-5 PMID: 16251969
  12. Determination of cell survival by RING-mediated regulation of inhibitor of apoptosis (IAP) protein abundance.
    Proc Natl Acad Sci U S A. 2005 Nov 8;102(45):16182-7 PMID: 16263936
  13. Unique proteasome subunit Xrpn10c is a specific receptor for the antiapoptotic ubiquitin-like protein Scythe.
    FEBS J. 2005 Dec;272(24):6373-86 PMID: 16336274
  14. ATP binding to PAN or the 26S ATPases causes association with the 20S proteasome, gate opening, and translocation of unfolded proteins.
    Mol Cell. 2005 Dec 9;20(5):687-98 PMID: 16337593
  15. Proteasome recruitment and activation of the Uch37 deubiquitinating enzyme by Adrm1.
    Nat Cell Biol. 2006 Sep;8(9):994-1002 PMID: 16906146
  16. A novel proteasome interacting protein recruits the deubiquitinating enzyme UCH37 to 26S proteasomes.
    EMBO J. 2006 Oct 4;25(19):4524-36 PMID: 16990800
  17. Proteasomal ubiquitin receptor RPN-10 controls sex determination in Caenorhabditis elegans.
    Mol Biol Cell. 2006 Dec;17(12):5356-71 PMID: 17050737
  18. hRpn13/ADRM1/GP110 is a novel proteasome subunit that binds the deubiquitinating enzyme, UCH37.
    EMBO J. 2006 Dec 13;25(24):5742-53 PMID: 17139257
  19. A ubiquitin stress response induces altered proteasome composition.
    Cell. 2007 May 18;129(4):747-59 PMID: 17512408
  20. Budding yeast Dsk2p is a polyubiquitin-binding protein that can interact with the proteasome.
    Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):745-50 PMID: 11805328
  21. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction.
    Physiol Rev. 2002 Apr;82(2):373-428 PMID: 11917093
  22. Ubiquitin-like proteins and Rpn10 play cooperative roles in ubiquitin-dependent proteolysis.
    Biochem Biophys Res Commun. 2002 May 10;293(3):986-92 PMID: 12051757
  23. Identification of ubiquitin-like protein-binding subunits of the 26S proteasome.
    Biochem Biophys Res Commun. 2002 Aug 30;296(4):813-9 PMID: 12200120
  24. Proteasome subunit Rpn1 binds ubiquitin-like protein domains.
    Nat Cell Biol. 2002 Sep;4(9):725-30 PMID: 12198498
  25. A cryptic protease couples deubiquitination and degradation by the proteasome.
    Nature. 2002 Sep 26;419(6905):403-7 PMID: 12353037
  26. Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome.
    Science. 2002 Oct 18;298(5593):611-5 PMID: 12183636
  27. Multiple associated proteins regulate proteasome structure and function.
    Mol Cell. 2002 Sep;10(3):495-507 PMID: 12408819
  28. Reverse genetic analysis of the Caenorhabditis elegans 26S proteasome subunits by RNA interference.
    Biol Chem. 2002 Jul-Aug;383(7-8):1263-6 PMID: 12437114
  29. Deletion of proteasomal subunit S5a/Rpn10/p54 causes lethality, multiple mitotic defects and overexpression of proteasomal genes in Drosophila melanogaster.
    J Cell Sci. 2003 Mar 15;116(Pt 6):1023-33 PMID: 12584246
  30. The pleiotropic role of the 26S proteasome subunit RPN10 in Arabidopsis growth and development supports a substrate-specific function in abscisic acid signaling.
    Plant Cell. 2003 Apr;15(4):965-80 PMID: 12671091
  31. Interaction of the anaphase-promoting complex/cyclosome and proteasome protein complexes with multiubiquitin chain-binding proteins.
    J Biol Chem. 2003 May 9;278(19):16791-6 PMID: 12615927
  32. Structural determinants for the binding of ubiquitin-like domains to the proteasome.
    EMBO J. 2003 Sep 15;22(18):4634-45 PMID: 12970176
  33. The ubiquitin-associated domain of hPLIC-2 interacts with the proteasome.
    Mol Biol Cell. 2003 Sep;14(9):3868-75 PMID: 12972570
  34. DNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a.
    Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12694-9 PMID: 14557549
  35. Involvement of the DNA repair protein hHR23 in p53 degradation.
    Mol Cell Biol. 2003 Dec;23(24):8960-9 PMID: 14645509
  36. Structure of the ubiquitin-interacting motif of S5a bound to the ubiquitin-like domain of HR23B.
    J Biol Chem. 2004 Feb 6;279(6):4760-7 PMID: 14585839
  37. Rad23 and Rpn10 serve as alternative ubiquitin receptors for the proteasome.
    J Biol Chem. 2004 Jun 25;279(26):26817-22 PMID: 15117949
  38. Multiple interactions of rad23 suggest a mechanism for ubiquitylated substrate delivery important in proteolysis.
    Mol Biol Cell. 2004 Jul;15(7):3357-65 PMID: 15121879
  39. Multiubiquitin chain receptors define a layer of substrate selectivity in the ubiquitin-proteasome system.
    Cell. 2004 Jul 9;118(1):99-110 PMID: 15242647
  40. GATA4 is essential for formation of the proepicardium and regulates cardiogenesis.
    Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12573-8 PMID: 15310850
  41. Ornithine decarboxylase is degraded by the 26S proteasome without ubiquitination.
    Nature. 1992 Dec 10;360(6404):597-9 PMID: 1334232
  42. A 26 S protease subunit that binds ubiquitin conjugates.
    J Biol Chem. 1994 Mar 11;269(10):7059-61 PMID: 8125911
  43. Efficient in vivo manipulation of mouse genomic sequences at the zygote stage.
    Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5860-5 PMID: 8650183
  44. The multiubiquitin-chain-binding protein Mcb1 is a component of the 26S proteasome in Saccharomyces cerevisiae and plays a nonessential, substrate-specific role in protein turnover.
    Mol Cell Biol. 1996 Nov;16(11):6020-8 PMID: 8887631
  45. Multiubiquitin chain binding and protein degradation are mediated by distinct domains within the 26 S proteasome subunit Mcb1.
    J Biol Chem. 1998 Jan 23;273(4):1970-81 PMID: 9442033
  46. The proteasome: paradigm of a self-compartmentalizing protease.
    Cell. 1998 Feb 6;92(3):367-80 PMID: 9476896
  47. Rad23 links DNA repair to the ubiquitin/proteasome pathway.
    Nature. 1998 Feb 12;391(6668):715-8 PMID: 9490418
  48. The MHC class I ligand-generating system: roles of immunoproteasomes and the interferon-gamma-inducible proteasome activator PA28.
    Immunol Rev. 1998 Jun;163:161-76 PMID: 9700509
  49. A subcomplex of the proteasome regulatory particle required for ubiquitin-conjugate degradation and related to the COP9-signalosome and eIF3.
    Cell. 1998 Sep 4;94(5):615-23 PMID: 9741626
  50. Developmentally regulated, alternative splicing of the Rpn10 gene generates multiple forms of 26S proteasomes.
    EMBO J. 2000 Aug 1;19(15):4144-53 PMID: 10921894
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.00509-07
Published
2007-10-00
Epub
2007-00-23
Pages
6629-38
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC2099239
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.00509-07 PMC Full Text View journal details
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