Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
AAAS Store

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 10 December 1999:
Vol. 286. no. 5447, pp. 2162 - 2165
DOI: 10.1126/science.286.5447.2162
Prev | Table of Contents | Next

Reports

Impaired Immunoproteasome Assembly and Immune Responses in PA28-/- Mice

Tobias Preckel, 1* Wai-Ping Fung-Leung, 1 Zeling Cai, 1 Antonella Vitiello, 1 Luisa Salter-Cid, 1 Ola Winqvist, 1dagger Tom G. Wolfe, 2 Matthias Von Herrath, 2 Ana Angulo, 2 Peter Ghazal, 2 Jiing-Dwan Lee, 2 Anne M. Fourie, 1 Ying Wu, 1 Jesse Pang, 1 Karen Ngo, 1 Per A. Peterson, 1 Klaus Früh, 1ddagger Young Yang 1ddagger

In vitro PA28 binds and activates proteasomes. It is shown here that mice with a disrupted PA28b gene lack PA28a and PA28b polypeptides, demonstrating that PA28 functions as a hetero-oligomer in vivo. Processing of antigenic epitopes derived from exogenous or endogenous antigens is altered in PA28-/- mice. Cytotoxic T lymphocyte responses are impaired, and assembly of immunoproteasomes is greatly inhibited in mice lacking PA28. These results show that PA28 is necessary for immunoproteasome assembly and is required for efficient antigen processing, thus demonstrating the importance of PA28-mediated proteasome function in immune responses.

1 The R. W. Johnson Pharmaceutical Research Institute, 3210 Merryfield Row, San Diego, CA 92121, USA.
2 The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA.
*   Present address: Agilent Technologies Deutschland GmbH, Hewlett Packard Strasse 8, 76337 Waldbronn, Germany.

dagger    Present address: University Hospital of Uppsala, Uppsala S-751 85, Sweden.

ddagger    To whom correspondence should be addressed. E-mail: kfrueh{at}prius.jnj.com (K.F.) or yyang{at}prius.jnj.com (Y.Y.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
UV-induced fragmentation of Cajal bodies.
M. Cioce, S. Boulon, A. G. Matera, and A. I. Lamond (2006)
J. Cell Biol. 175, 401-413
   Abstract »    Full Text »    PDF »
Proteasome Activator PA200 Is Required for Normal Spermatogenesis.
B. Khor, A. L. Bredemeyer, C.-Y. Huang, I. R. Turnbull, R. Evans, L. B. Maggi Jr., J. M. White, L. M. Walker, K. Carnes, R. A. Hess, et al. (2006)
Mol. Cell. Biol. 26, 2999-3007
   Abstract »    Full Text »    PDF »
IFN-{gamma}-Primed Macrophages Exhibit Increased CCR2-Dependent Migration and Altered IFN-{gamma} Responses Mediated by Stat1.
X. Hu, K.-H. Park-Min, H. H. Ho, and L. B. Ivashkiv (2005)
J. Immunol. 175, 3637-3647
   Abstract »    Full Text »    PDF »
Mutant SOD1 alters the motor neuronal transcriptome: implications for familial ALS.
J. Kirby, E. Halligan, M. J. Baptista, S. Allen, P. R. Heath, H. Holden, S. C. Barber, C. A. Loynes, C. A. Wood-Allum, J. Lunec, et al. (2005)
Brain 128, 1686-1706
   Abstract »    Full Text »    PDF »
Immunoproteasomes Down-Regulate Presentation of a Subdominant T Cell Epitope from Lymphocytic Choriomeningitis Virus.
M. Basler, N. Youhnovski, M. van den Broek, M. Przybylski, and M. Groettrup (2004)
J. Immunol. 173, 3925-3934
   Abstract »    Full Text »    PDF »
Immune Defects in 28-kDa Proteasome Activator {gamma}-Deficient Mice.
L. F. Barton, H. A. Runnels, T. D. Schell, Y. Cho, R. Gibbons, S. S. Tevethia, G. S. Deepe Jr., and J. J. Monaco (2004)
J. Immunol. 172, 3948-3954
   Abstract »    Full Text »    PDF »
Immunoproteomics: Mass Spectrometry-based Methods to Study the Targets of the Immune Response.
A. W. Purcell and J. J. Gorman (2004)
Mol. Cell. Proteomics 3, 193-208
   Abstract »    Full Text »    PDF »
A Cytomegalovirus Inhibitor of Gamma Interferon Signaling Controls Immunoproteasome Induction.
S. Khan, A. Zimmermann, M. Basler, M. Groettrup, and H. Hengel (2004)
J. Virol. 78, 1831-1842
   Abstract »    Full Text »    PDF »
Drosophila ventral furrow morphogenesis: a proteomic analysis.
L. Gong, M. Puri, M. Unlu, M. Young, K. Robertson, S. Viswanathan, A. Krishnaswamy, S. R. Dowd, and J. S. Minden (2004)
Development 131, 643-656
   Abstract »    Full Text »    PDF »
The Proteasome as a Lipopolysaccharide-Binding Protein in Macrophages: Differential Effects of Proteasome Inhibition on Lipopolysaccharide-Induced Signaling Events.
N. Qureshi, P.-Y. Perera, J. Shen, G. Zhang, A. Lenschat, G. Splitter, D. C. Morrison, and S. N. Vogel (2003)
J. Immunol. 171, 1515-1525
   Abstract »    Full Text »    PDF »
Biochemical Analysis of the 20 S Proteasome of Trypanosoma brucei.
C. C. Wang, Z. Bozdech, C.-l. Liu, A. Shipway, B. J. Backes, J. L. Harris, and M. Bogyo (2003)
J. Biol. Chem. 278, 15800-15808
   Abstract »    Full Text »    PDF »
Differential Expression of Tapasin and Immunoproteasome Subunits in Adenovirus Type 5- Versus Type 12-transformed Cells.
A. C. O. Vertegaal, H. B. Kuiperij, A. Houweling, M. Verlaan, A. J. van der Eb, and A. Zantema (2003)
J. Biol. Chem. 278, 139-146
   Abstract »    Full Text »    PDF »
Functional Characterization of the 11 Non-ATPase Subunit Proteins in the Trypanosome 19 S Proteasomal Regulatory Complex.
Z. Li and C. C. Wang (2002)
J. Biol. Chem. 277, 42686-42693
   Abstract »    Full Text »    PDF »
PI31 is a modulator of proteasome formation and antigen processing.
D. M. W. Zaiss, S. Standera, P.-M. Kloetzel, and A. J. A. M. Sijts (2002)
PNAS 99, 14344-14349
   Abstract »    Full Text »    PDF »
Two Distinct Pathways Mediated by PA28 and hsp90 in Major Histocompatibility Complex Class I Antigen Processing.
T. Yamano, S. Murata, N. Shimbara, N. Tanaka, T. Chiba, K. Tanaka, K. Yui, and H. Udono (2002)
J. Exp. Med. 196, 185-196
   Abstract »    Full Text »    PDF »
An Easily Dissociated 26 S Proteasome Catalyzes an Essential Ubiquitin-mediated Protein Degradation Pathway in Trypanosoma brucei.
Z. Li, C.-B. Zou, Y. Yao, M. A. Hoyt, S. McDonough, Z. B. Mackey, P. Coffino, and C. C. Wang (2002)
J. Biol. Chem. 277, 15486-15498
   Abstract »    Full Text »    PDF »
Expression of the Proteasome Activator PA28 Rescues the Presentation of a Cytotoxic T Lymphocyte Epitope on Melanoma Cells.
Y. Sun, A. J. A. M. Sijts, M. Song, K. Janek, A. K. Nussbaum, S. Kral, M. Schirle, S. Stevanovic, A. Paschen, H. Schild, et al. (2002)
Cancer Res. 62, 2875-2882
   Abstract »    Full Text »    PDF »
Immunoproteasomes Largely Replace Constitutive Proteasomes During an Antiviral and Antibacterial Immune Response in the Liver.
S. Khan, M. van den Broek, K. Schwarz, R. de Giuli, P.-A. Diener, and M. Groettrup (2001)
J. Immunol. 167, 6859-6868
   Abstract »    Full Text »    PDF »
Bipartite regulation of different components of the MHC class I antigen-processing machinery during dendritic cell maturation.
J. Li, B. Schuler-Thurner, G. Schuler, C. Huber, and B. Seliger (2001)
Int. Immunol. 13, 1515-1523
   Abstract »    Full Text »    PDF »
The Murine Cytomegalovirus pp89 Immunodominant H-2Ld Epitope Is Generated and Translocated into the Endoplasmic Reticulum as an 11-Mer Precursor Peptide.
C. Knuehl, P. Spee, T. Ruppert, U. Kuckelkorn, P. Henklein, J. Neefjes, and P.-M. Kloetzel (2001)
J. Immunol. 167, 1515-1521
   Abstract »    Full Text »    PDF »
Interferon gamma regulates accumulation of the proteasome activator PA28 and immunoproteasomes at nuclear PML bodies.
R. Fabunmi, W. Wigley, P. Thomas, and G. DeMartino (2001)
J. Cell Sci. 114, 29-36
   Abstract »    PDF »
Factors Controlling the Trafficking and Processing of a Leader-Derived Peptide Presented by Qa-1.
A. Bai, C. J. Aldrich, and J. Forman (2000)
J. Immunol. 165, 7025-7034
   Abstract »    Full Text »    PDF »
Differential Influence on Cytotoxic T Lymphocyte Epitope Presentation by Controlled Expression of Either Proteasome Immunosubunits or PA28.
T. van Hall, A. Sijts, M. Camps, R. Offringa, C. Melief, P.-M. Kloetzel, and F. Ossendorp (2000)
J. Exp. Med. 192, 483-494
   Abstract »    Full Text »    PDF »
Hybrid Proteasomes. INDUCTION BY INTERFERON-gamma AND CONTRIBUTION TO ATP-DEPENDENT PROTEOLYSIS.
N. Tanahashi, Y. Murakami, Y. Minami, N. Shimbara, K. B. Hendil, and K. Tanaka (2000)
J. Biol. Chem. 275, 14336-14345
   Abstract »    Full Text »    PDF »
cDNA Cloning, Expression, and Functional Characterization of PI31, a Proline-rich Inhibitor of the Proteasome.
S. L. McCutchen-Maloney, K. Matsuda, N. Shimbara, D. D. Binns, K. Tanaka, C. A. Slaughter, and G. N. DeMartino (2000)
J. Biol. Chem. 275, 18557-18565
   Abstract »    Full Text »    PDF »
Novel Propeptide Function in 20 S Proteasome Assembly Influences beta Subunit Composition.
D. J. Kingsbury, T. A. Griffin, and R. A. Colbert (2000)
J. Biol. Chem. 275, 24156-24162
   Abstract »    Full Text »    PDF »
Identification and Characterization of a Drosophila Nuclear Proteasome Regulator. A HOMOLOG OF HUMAN 11 S REGgamma (PA28gamma ).
P. Masson, O. Andersson, U.-M. Petersen, and P. Young (2001)
J. Biol. Chem. 276, 1383-1390
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products