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.

Subscribe

Logo for

Science 322 (5904): 1104-1107

Copyright © 2008 by the American Association for the Advancement of Science

Ubiquitin-Like Protein Involved in the Proteasome Pathway of Mycobacterium tuberculosis

Michael J. Pearce,1 Julian Mintseris,2 Jessica Ferreyra,1 Steven P. Gygi,2 K. Heran Darwin1*

Abstract: The protein modifier ubiquitin is a signal for proteasome-mediated degradation in eukaryotes. Proteasome-bearing prokaryotes have been thought to degrade proteins via a ubiquitin-independent pathway. We have identified a prokaryotic ubiquitin-like protein, Pup (Rv2111c), which was specifically conjugated to proteasome substrates in the pathogen Mycobacterium tuberculosis. Pupylation occurred on lysines and required proteasome accessory factor A (PafA). In a pafA mutant, pupylated proteins were absent and substrates accumulated, thereby connecting pupylation with degradation. Although analogous to ubiquitylation, pupylation appears to proceed by a different chemistry. Thus, like eukaryotes, bacteria may use a small-protein modifier to control protein stability.

1 Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
2 Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

* To whom correspondence should be addressed. E-mail: heran.darwin{at}med.nyu.edu


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Survival of mycobacteria depends on proteasome-mediated amino acid recycling under nutrient limitation.
Y. Elharar, Z. Roth, I. Hermelin, A. Moon, G. Peretz, Y. Shenkerman, M. Vishkautzan, I. Khalaila, and E. Gur (2014)
EMBO J.
   Abstract »    Full Text »    PDF »
Proteome-wide identification of mycobacterial pupylation targets.
C. Poulsen, Y. Akhter, A. H.-W. Jeon, G. Schmitt-Ulms, H. E. Meyer, A. Stefanski, K. Stuhler, M. Wilmanns, and Y.-H. Song (2014)
Mol Syst Biol 6, 386
   Abstract »    Full Text »    PDF »
CPLM: a database of protein lysine modifications.
Z. Liu, Y. Wang, T. Gao, Z. Pan, H. Cheng, Q. Yang, Z. Cheng, A. Guo, J. Ren, and Y. Xue (2014)
Nucleic Acids Res. 42, D531-D536
   Abstract »    Full Text »    PDF »
Allosteric Transitions Direct Protein Tagging by PafA, the Prokaryotic Ubiquitin-like Protein (Pup) Ligase.
N. Ofer, N. Forer, M. Korman, M. Vishkautzan, I. Khalaila, and E. Gur (2013)
J. Biol. Chem. 288, 11287-11293
   Abstract »    Full Text »    PDF »
Molecular Regulation of Antibiotic Biosynthesis in Streptomyces.
G. Liu, K. F. Chater, G. Chandra, G. Niu, and H. Tan (2013)
Microbiol. Mol. Biol. Rev. 77, 112-143
   Abstract »    Full Text »    PDF »
Characterizing Ubiquitination Sites by Peptide-based Immunoaffinity Enrichment.
D. Bustos, C. E. Bakalarski, Y. Yang, J. Peng, and D. S. Kirkpatrick (2012)
Mol. Cell. Proteomics 11, 1529-1540
   Abstract »    Full Text »    PDF »
The Archaeal Proteasome Is Regulated by a Network of AAA ATPases.
D. Forouzan, M. Ammelburg, C. F. Hobel, L. J. Stroh, N. Sessler, J. Martin, and A. N. Lupas (2012)
J. Biol. Chem. 287, 39254-39262
   Abstract »    Full Text »    PDF »
Mycobacterium tuberculosis Prokaryotic Ubiquitin-like Protein-deconjugating Enzyme Is an Unusual Aspartate Amidase.
K. E. Burns, F. E. McAllister, C. Schwerdtfeger, J. Mintseris, F. Cerda-Maira, E. E. Noens, M. Wilmanns, S. R. Hubbard, F. Melandri, H. Ovaa, et al. (2012)
J. Biol. Chem. 287, 37522-37529
   Abstract »    Full Text »    PDF »
The Expanding Universe of Ubiquitin and Ubiquitin-Like Modifiers.
R. D. Vierstra (2012)
Plant Physiology 160, 2-14
   Full Text »    PDF »
An Ancient Portal to Proteolysis.
A. Matouschek and D. Finley (2012)
Science 337, 813-814
   Abstract »    Full Text »    PDF »
Diversity in Genetic In Vivo Methods for Protein-Protein Interaction Studies: from the Yeast Two-Hybrid System to the Mammalian Split-Luciferase System.
B. Stynen, H. Tournu, J. Tavernier, and P. Van Dijck (2012)
Microbiol. Mol. Biol. Rev. 76, 331-382
   Abstract »    Full Text »    PDF »
Posttranslational Modification of Cellular Proteins by a Ubiquitin-like Protein in Bacteria.
N. Shigi (2012)
J. Biol. Chem. 287, 17568-17577
   Abstract »    Full Text »    PDF »
Activity of the Mycobacterial Proteasomal ATPase Mpa Is Reversibly Regulated by Pupylation.
C. L. Delley, F. Striebel, F. M. Heydenreich, D. Ozcelik, and E. Weber-Ban (2012)
J. Biol. Chem. 287, 7907-7914
   Abstract »    Full Text »    PDF »
Metabolic Switches and Adaptations Deduced from the Proteomes of Streptomyces coelicolor Wild Type and phoP Mutant Grown in Batch Culture.
L. Thomas, D. A. Hodgson, A. Wentzel, K. Nieselt, T. E. Ellingsen, J. Moore, E. R. Morrissey, R. Legaie, The STREAM Consortium, W. Wohlleben, et al. (2012)
Mol. Cell. Proteomics 11, M111.013797
   Abstract »    Full Text »    PDF »
A unique homologue of the eukaryotic protein-modifier ubiquitin present in the bacterium Bacteroides fragilis, a predominant resident of the human gastrointestinal tract.
S. Patrick, K. L. Jobling, D. O'Connor, Z. Thacker, D. T. F. Dryden, and G. W. Blakely (2011)
Microbiology 157, 3071-3078
   Abstract »    Full Text »    PDF »
Reconstitution of the Mycobacterium tuberculosis pupylation pathway in Escherichia coli.
F. A. Cerda-Maira, F. McAllister, N. J. Bode, K. E. Burns, S. P. Gygi, and K. H. Darwin (2011)
EMBO Rep. 12, 863-870
   Abstract »    Full Text »    PDF »
Insights into the evolution of Archaea and eukaryotic protein modifier systems revealed by the genome of a novel archaeal group.
T. Nunoura, Y. Takaki, J. Kakuta, S. Nishi, J. Sugahara, H. Kazama, G.-J. Chee, M. Hattori, A. Kanai, H. Atomi, et al. (2011)
Nucleic Acids Res. 39, 3204-3223
   Abstract »    Full Text »    PDF »
Mycobacterial Ubiquitin-like Protein Ligase PafA Follows a Two-step Reaction Pathway with a Phosphorylated Pup Intermediate.
E. Guth, M. Thommen, and E. Weber-Ban (2011)
J. Biol. Chem. 286, 4412-4419
   Abstract »    Full Text »    PDF »
Dop functions as a depupylase in the prokaryotic ubiquitin-like modification pathway.
F. Imkamp, F. Striebel, M. Sutter, D. Ozcelik, N. Zimmermann, P. Sander, and E. Weber-Ban (2010)
EMBO Rep. 11, 791-797
   Abstract »    Full Text »    PDF »
cAMP-regulated Protein Lysine Acetylases in Mycobacteria.
S. Nambi, N. Basu, and S. S. Visweswariah (2010)
J. Biol. Chem. 285, 24313-24323
   Abstract »    Full Text »    PDF »
Prokaryotic Ubiquitin-Like Protein Provides a Two-Part Degron to Mycobacterium Proteasome Substrates.
K. E. Burns, M. J. Pearce, and K. H. Darwin (2010)
J. Bacteriol. 192, 2933-2935
   Abstract »    Full Text »    PDF »
Pup grows up: in vitro characterization of the degradation of pupylated proteins.
D. A. Kraut and A. Matouschek (2010)
EMBO J. 29, 1163-1164
   Abstract »    Full Text »    PDF »
The mycobacterial Mpa-proteasome unfolds and degrades pupylated substrates by engaging Pup's N-terminus.
F. Striebel, M. Hunkeler, H. Summer, and E. Weber-Ban (2010)
EMBO J. 29, 1262-1271
   Abstract »    Full Text »    PDF »
The family of ubiquitin-conjugating enzymes (E2s): deciding between life and death of proteins.
S. J. L. van Wijk and H. T. M. Timmers (2010)
FASEB J 24, 981-993
   Abstract »    Full Text »    PDF »
Degradation of an intramitochondrial protein by the cytosolic proteasome.
V. Azzu and M. D. Brand (2010)
J. Cell Sci. 123, 578-585
   Abstract »    Full Text »    PDF »
How the MccB bacterial ancestor of ubiquitin E1 initiates biosynthesis of the microcin C7 antibiotic.
C. A. Regni, R. F. Roush, D. J. Miller, A. Nourse, C. T. Walsh, and B. A. Schulman (2009)
EMBO J. 28, 1953-1964
   Abstract »    Full Text »    PDF »
Proteasomal Protein Degradation in Mycobacteria Is Dependent upon a Prokaryotic Ubiquitin-like Protein.
K. E. Burns, W.-T. Liu, H. I. M. Boshoff, P. C. Dorrestein, and C. E. Barry 3rd (2009)
J. Biol. Chem. 284, 3069-3075
   Abstract »    Full Text »    PDF »
MICROBIOLOGY: A Protein Pupylation Paradigm.
S. Mukherjee and K. Orth (2008)
Science 322, 1062-1063
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882