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Science 5 May 1995:
Vol. 268. no. 5211, pp. 726 - 731
DOI: 10.1126/science.7732382
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Articles

Science, Vol 268, Issue 5211, 726-731
Copyright © 1995 by American Association for the Advancement of Science

articles

Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin

G Fenteany, RF Standaert, WS Lane, S Choi, EJ Corey, and SL Schreiber

Howard Hughes Medical Institute, Department of Chemistry, Harvard University, Cambridge, MA 02138.

Lactacystin is a Streptomyces metabolite that inhibits cell cycle progression and induces neurite outgrowth in a murine neuroblastoma cell line. Tritium-labeled lactacystin was used to identify the 20S proteasome as its specific cellular target. Three distinct peptidase activities of this enzyme complex (trypsin-like, chymotrypsin-like, and peptidylglutamyl-peptide hydrolyzing activities) were inhibited by lactacystin, the first two irreversibly and all at different rates. None of five other proteases were inhibited, and the ability of lactacystin analogs to inhibit cell cycle progression and induce neurite outgrowth correlated with their ability to inhibit the proteasome. Lactacystin appears to modify covalently the highly conserved amino-terminal threonine of the mammalian proteasome subunit X (also called MB1), a close homolog of the LMP7 proteasome subunit encoded by the major histocompatibility complex. This threonine residue may therefore have a catalytic role, and subunit X/MB1 may be a core component of an amino-terminal-threonine protease activity of the proteasome.


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Preservation of Caspase-3 Subunits from Degradation Contributes to Apoptosis Evoked by Lactacystin: Any Single Lysine or Lysine Pair of the Small Subunit Is Sufficient for Ubiquitination.
L. Chen, L. Smith, Z. Wang, and J. B. Smith (2003)
Mol. Pharmacol. 64, 334-345
   Abstract »    Full Text »    PDF »
The Inhibition of Early N-Glycan Processing Targets TRP-2 to Degradation in B16 Melanoma Cells.
G. Negroiu, R. A. Dwek, and S. M. Petrescu (2003)
J. Biol. Chem. 278, 27035-27042
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Elucidation of the molecular logic by which misfolded {alpha}1-antitrypsin is preferentially selected for degradation.
Y. Wu, M. T. Swulius, K. W. Moremen, and R. N. Sifers (2003)
PNAS 100, 8229-8234
   Abstract »    Full Text »    PDF »
Mitotic and Stress-induced Phosphorylation of HsPI3K-C2{alpha} Targets the Protein for Degradation.
S. A. Didichenko, C. M. Fragoso, and M. Thelen (2003)
J. Biol. Chem. 278, 26055-26064
   Abstract »    Full Text »    PDF »
Characterization of the expression of the hepatitis C virus F protein.
J. Roussel, A. Pillez, C. Montpellier, G. Duverlie, A. Cahour, J. Dubuisson, and C. Wychowski (2003)
J. Gen. Virol. 84, 1751-1759
   Abstract »    Full Text »    PDF »
Rapid Turnover of Extracellular Signal-Regulated Kinase 3 by the Ubiquitin-Proteasome Pathway Defines a Novel Paradigm of Mitogen-Activated Protein Kinase Regulation during Cellular Differentiation.
P. Coulombe, G. Rodier, S. Pelletier, J. Pellerin, and S. Meloche (2003)
Mol. Cell. Biol. 23, 4542-4558
   Abstract »    Full Text »    PDF »
Inhibition of the Proteasome by Lactacystin Enhances Oligodendroglial Cell Differentiation.
L. A. Pasquini, P. M. Paez, M. A. N. B. Moreno, J. M. Pasquini, and E. F. Soto (2003)
J. Neurosci. 23, 4635-4644
   Abstract »    Full Text »    PDF »
A tyrosine-based sorting signal is involved in connexin43 stability and gap junction turnover.
M. A. Thomas, N. Zosso, I. Scerri, N. Demaurex, M. Chanson, and O. Staub (2003)
J. Cell Sci. 116, 2213-2222
   Abstract »    Full Text »    PDF »
Lithium Stabilizes the CCAAT/Enhancer-binding Protein {alpha} (C/EBP{alpha}) through a Glycogen Synthase Kinase 3 (GSK3)-independent Pathway Involving Direct Inhibition of Proteasomal Activity.
M. Shim and R. C. Smart (2003)
J. Biol. Chem. 278, 19674-19681
   Abstract »    Full Text »    PDF »
Participation of the sperm proteasome in human fertilization.
P. Morales, M. Kong, E. Pizarro, and C. Pasten (2003)
Hum. Reprod. 18, 1010-1017
   Abstract »    Full Text »    PDF »
From the Cover: Clathrin-coated pits with long, dynamin-wrapped necks upon expression of a clathrin antisense RNA.
T.-G. Iversen, G. Skretting, B. van Deurs, and K. Sandvig (2003)
PNAS 100, 5175-5180
   Abstract »    Full Text »    PDF »
Conditional Knockdown of Proteasomes Results in Cell-cycle Arrest and Enhanced Expression of Molecular Chaperones Hsp70 and Hsp40 in Chicken DT40 Cells.
T. Tanahashi-Hori, N. Tanahashi, K. Tanaka, and T. Chiba (2003)
J. Biol. Chem. 278, 16237-16243
   Abstract »    Full Text »    PDF »
Identification of a TAP-Independent, Immunoproteasome-Dependent CD8+ T-Cell Epitope in Epstein-Barr Virus Latent Membrane Protein 2.
G. Lautscham, T. Haigh, S. Mayrhofer, G. Taylor, D. Croom-Carter, A. Leese, S. Gadola, V. Cerundolo, A. Rickinson, and N. Blake (2003)
J. Virol. 77, 2757-2761
   Abstract »    Full Text »    PDF »
Cyclin-Dependent Kinase Activity Is Required for Apoptotic Death But Not Inclusion Formation in Cortical Neurons after Proteasomal Inhibition.
H. J. Rideout, Q. Wang, D. S. Park, and L. Stefanis (2003)
J. Neurosci. 23, 1237-1245
   Abstract »    Full Text »    PDF »
Fusion with HDEL Protects Cell Wall Invertase from Early Degradation when N-glycosylation is Inhibited.
S. Pagny, L.-A. Denmat-Ouisse, V. Gomord, and L. Faye (2003)
Plant Cell Physiol. 44, 173-182
   Abstract »    Full Text »    PDF »
Proteasome Inhibition Results in TRAIL Sensitization of Primary Keratinocytes by Removing the Resistance-Mediating Block of Effector Caspase Maturation.
M. Leverkus, M. R. Sprick, T. Wachter, T. Mengling, B. Baumann, E. Serfling, E.-B. Brocker, M. Goebeler, M. Neumann, and H. Walczak (2003)
Mol. Cell. Biol. 23, 777-790
   Abstract »    Full Text »
The Carboxy Terminus of Prospero Regulates Its Subcellular Localization.
X. Bi, A. V. Kajava, T. Jones, Z. N. Demidenko, and M. A. Mortin (2003)
Mol. Cell. Biol. 23, 1014-1024
   Abstract »    Full Text »
Subunit Topology of Two 20S Proteasomes from Haloferax volcanii.
S. J. Kaczowka and J. A. Maupin-Furlow (2003)
J. Bacteriol. 185, 165-174
   Abstract »    Full Text »    PDF »


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