![]()
|
|
||||||||
J. Biol. Chem., Vol. 276, Issue 30, 27936-27943, July 27, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Biochemistry and Molecular Biology, School
of Public Health, Johns Hopkins University,
Baltimore, Maryland 21205
Polyubiquitin chains assembled through lysine 48 (Lys-48) of ubiquitin act as a signal for substrate proteolysis by 26 S
proteasomes, whereas chains assembled through Lys-63 play a
mechanistically undefined role in post-replicative DNA repair. We
showed previously that the products of the UBC13 and
MMS2 genes function in error-free post-replicative DNA
repair in the yeast Saccharomyces cerevisiae and form a
complex that assembles Lys-63-linked polyubiquitin chains in
vitro. Here we confirm that the Mms2·Ubc13 complex functions as
a high affinity heterodimer in the chain assembly reaction in
vitro and report the results of a kinetic characterization of the
polyubiquitin chain assembly reaction. To test whether a Lys-63-linked
polyubiquitin chain can signal degradation, we conjugated Lys-63-linked
tetra-ubiquitin to a model substrate of 26 S proteasomes. Although the
noncanonical chain effectively signaled substrate degradation, the
results of new genetic epistasis studies agree with previous genetic
data in suggesting that the proteolytic activity of proteasomes is not
required for error-free post-replicative repair.
In Vitro Assembly and Recognition of Lys-63
Polyubiquitin Chains*
and
*
This work was supported by National Institutes of Health
(NIH) Grant GM60372 and by a training grant from the NIEHS, NIH.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present address: Laboratory of Synthetic Protein Chemistry, The
Rockefeller University, New York, NY 10021.
This article has been cited by other articles:
![]() |
R. Wen, J. A. Torres-Acosta, L. Pastushok, X. Lai, L. Pelzer, H. Wang, and W. Xiao Arabidopsis UEV1D Promotes Lysine-63-Linked Polyubiquitination and Is Involved in DNA Damage Response PLANT CELL, January 1, 2008; 20(1): 213 - 227. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Barriere, C. Nemes, K. Du, and G. L. Lukacs Plasticity of Polyubiquitin Recognition as Lysosomal Targeting Signals by the Endosomal Sorting Machinery Mol. Biol. Cell, October 1, 2007; 18(10): 3952 - 3965. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. T. Kim, K. P. Kim, F. Lledias, A. F. Kisselev, K. M. Scaglione, D. Skowyra, S. P. Gygi, and A. L. Goldberg Certain Pairs of Ubiquitin-conjugating Enzymes (E2s) and Ubiquitin-Protein Ligases (E3s) Synthesize Nondegradable Forked Ubiquitin Chains Containing All Possible Isopeptide Linkages J. Biol. Chem., June 15, 2007; 282(24): 17375 - 17386. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. P. Marx, A. S. Soehn, D. Berg, C. Melle, C. Schiesling, M. Lang, S. Kautzmann, K. M. Strauss, T. Franck, S. Engelender, et al. The proteasomal subunit S6 ATPase is a novel synphilin-1 interacting protein--implications for Parkinson's disease FASEB J, June 1, 2007; 21(8): 1759 - 1767. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Dreher and J. Callis Ubiquitin, Hormones and Biotic Stress in Plants Ann. Bot., May 1, 2007; 99(5): 787 - 822. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Fukushima, S.-i. Matsuzawa, C. L. Kress, J. M. Bruey, M. Krajewska, S. Lefebvre, J. M. Zapata, Z. Ronai, and J. C. Reed Ubiquitin-conjugating enzyme Ubc13 is a critical component of TNF receptor-associated factor (TRAF)-mediated inflammatory responses PNAS, April 10, 2007; 104(15): 6371 - 6376. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Tuvia, D. Taglicht, O. Erez, I. Alroy, I. Alchanati, V. Bicoviski, M. Dori-Bachash, D. Ben-Avraham, and Y. Reiss The ubiquitin E3 ligase POSH regulates calcium homeostasis through spatial control of Herp J. Cell Biol., April 9, 2007; 177(1): 51 - 61. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Kunze, D. MacCallum, F. C. Odds, and B. Hube Multiple functions of DOA1 in Candida albicans Microbiology, April 1, 2007; 153(4): 1026 - 1041. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. T. Lis and F. E. Romesberg Role of Doa1 in the Saccharomyces cerevisiae DNA Damage Response. Mol. Cell. Biol., June 1, 2006; 26(11): 4122 - 4133. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Kim and H. Rao What's Ub Chain Linkage Got to Do with It? Sci. Signal., April 11, 2006; 2006(330): pe18 - pe18. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Okumura, G. Lu, I. Pitha-Rowe, and P. M. Pitha Innate antiviral response targets HIV-1 release by the induction of ubiquitin-like protein ISG15 PNAS, January 31, 2006; 103(5): 1440 - 1445. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Shang, G. Deng, Q. Liu, W. Guo, A. L. Haas, B. Crosas, D. Finley, and A. Taylor Lys6-modified Ubiquitin Inhibits Ubiquitin-dependent Protein Degradation J. Biol. Chem., May 27, 2005; 280(21): 20365 - 20374. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Tsui, A. Raguraj, and C. M. Pickart Ubiquitin Binding Site of the Ubiquitin E2 Variant (UEV) Protein Mms2 Is Required for DNA Damage Tolerance in the Yeast RAD6 Pathway J. Biol. Chem., May 20, 2005; 280(20): 19829 - 19835. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. W. Doss-Pepe, L. Chen, and K. Madura {alpha}-Synuclein and Parkin Contribute to the Assembly of Ubiquitin Lysine 63-linked Multiubiquitin Chains J. Biol. Chem., April 29, 2005; 280(17): 16619 - 16624. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Laine and Z. Ronai Ubiquitin Chains in the Ladder of MAPK Signaling Sci. Signal., April 26, 2005; 2005(281): re5 - re5. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Huang, Q. Huang, X. Zhou, M. M. Shen, A. Yen, S. X. Yu, G. Dong, K. Qu, P. Huang, E. M. Anderson, et al. The Poxvirus p28 Virulence Factor Is an E3 Ubiquitin Ligase J. Biol. Chem., December 24, 2004; 279(52): 54110 - 54116. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Tenno, K. Fujiwara, H. Tochio, K. Iwai, E. H. Morita, H. Hayashi, S. Murata, H. Hiroaki, M. Sato, K. Tanaka, et al. Structural basis for distinct roles of Lys63- and Lys48-linked polyubiquitin chains Genes Cells, October 1, 2004; 9(10): 865 - 875. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. L. Seibenhener, J. R. Babu, T. Geetha, H. C. Wong, N. R. Krishna, and M. W. Wooten Sequestosome 1/p62 Is a Polyubiquitin Chain Binding Protein Involved in Ubiquitin Proteasome Degradation Mol. Cell. Biol., September 15, 2004; 24(18): 8055 - 8068. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Matsusaka and J. Pines Chfr acts with the p38 stress kinases to block entry to mitosis in mammalian cells J. Cell Biol., August 16, 2004; 166(4): 507 - 516. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. L. Ramsey, J. J. Smith, A. Dasgupta, N. Maqani, P. Grant, and D. T. Auble The NEF4 Complex Regulates Rad4 Levels and Utilizes Snf2/Swi2-Related ATPase Activity for Nucleotide Excision Repair Mol. Cell. Biol., July 15, 2004; 24(14): 6362 - 6378. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Kim, K. Mi, and H. Rao Multiple Interactions of Rad23 Suggest a Mechanism for Ubiquitylated Substrate Delivery Important in Proteolysis Mol. Biol. Cell, July 1, 2004; 15(7): 3357 - 3365. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Varadan, M. Assfalg, A. Haririnia, S. Raasi, C. Pickart, and D. Fushman Solution Conformation of Lys63-linked Di-ubiquitin Chain Provides Clues to Functional Diversity of Polyubiquitin Signaling J. Biol. Chem., February 20, 2004; 279(8): 7055 - 7063. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Didier, L. Broday, A. Bhoumik, S. Israeli, S. Takahashi, K. Nakayama, S. M. Thomas, C. E. Turner, S. Henderson, H. Sabe, et al. RNF5, a RING Finger Protein That Regulates Cell Motility by Targeting Paxillin Ubiquitination and Altered Localization Mol. Cell. Biol., August 1, 2003; 23(15): 5331 - 5345. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Raasi and C. M. Pickart Rad23 Ubiquitin-associated Domains (UBA) Inhibit 26 S Proteasome-catalyzed Proteolysis by Sequestering Lysine 48-linked Polyubiquitin Chains J. Biol. Chem., March 7, 2003; 278(11): 8951 - 8959. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. D. Ulrich Protein-Protein Interactions within an E2-RING Finger Complex. IMPLICATIONS FOR UBIQUITIN-DEPENDENT DNA DAMAGE REPAIR J. Biol. Chem., February 21, 2003; 278(9): 7051 - 7058. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Alberti, J. Demand, C. Esser, N. Emmerich, H. Schild, and J. Hohfeld Ubiquitylation of BAG-1 Suggests a Novel Regulatory Mechanism during the Sorting of Chaperone Substrates to the Proteasome J. Biol. Chem., November 22, 2002; 277(48): 45920 - 45927. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Kiakos, T. T. Howard, M. Lee, J. A. Hartley, and P. J. McHugh Saccharomyces cerevisiae RAD5 Influences the Excision Repair of DNA Minor Groove Adducts J. Biol. Chem., November 8, 2002; 277(46): 44576 - 44581. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Rao and A. Sastry Recognition of Specific Ubiquitin Conjugates Is Important for the Proteolytic Functions of the Ubiquitin-associated Domain Proteins Dsk2 and Rad23 J. Biol. Chem., March 29, 2002; 277(14): 11691 - 11695. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. D. Ulrich Degradation or Maintenance: Actions of the Ubiquitin System on Eukaryotic Chromatin Eukaryot. Cell, February 1, 2002; 1(1): 1 - 10. [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |