JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on April 5, 2002
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
277/15/12632    most recent
M111830200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Borra, M. T.
Right arrow Articles by Denu, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Borra, M. T.
Right arrow Articles by Denu, J. M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Papers In Press, published online ahead of print January 25, 2002
J. Biol. Chem, 10.1074/jbc.M111830200
Submitted on December 12, 2001
Revised on January 25, 2002
Accepted on January 25, 2002

Conserved enzymatic production and biological effect of O-acetyl ADP ribose by Sir2-like NAD+-dependent deacteylases

Margie T. Borra, Forest J. O'Neill, Michael D. Jackson, Brett Marshall, Eric Verdin, Kathy R. Foltz, and John M. Denu

Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland, OR 97201

Corresponding Author: denuj{at}ohsu.edu

Silent information regulator 2 (Sir2) family of enzymes has been implicated in many cellular processes that include histone deacetylation, gene silencing, chromosomal stability and aging. Yeast Sir2 and several homologues have been shown to be NAD+-dependent histone/protein deacetylases. Previously, it was demonstrated that the yeast enzymes catalyze a unique reaction mechanism in which the cleavage of NAD+ and the deacetylation of substrate are coupled with the formation of O-acetyl-ADP-ribose, a novel metabolite. Here, we demonstrate that the production of O-acetyl-ADP-ribose is evolutionarily conserved among Sir2-like enzymes from yeast, Drosophila and human. Also, endogenous yeast Sir2 complex from telomeres was shown to generate O-acetyl-ADP-ribose. Using a quantitative microinjection assay to examine the possible biological function(s) of this newly discovered metabolite, we demonstrate that O-acetyl-ADP-ribose causes a delay/block in oocyte maturation, and results in a delay/block in embryo cell division in blastomeres. This effect was mimicked by injection of low nanoM levels of active enzyme, but not with a catalytically impaired mutant, indicating that the enzymatic activity is essential for the observed effects. In cell-free oocyte extracts, we demonstrate the existence of cellular enzymes that can efficiently utilize O-acetyl-ADP-ribose.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
T. M. Kowieski, S. Lee, and J. M. Denu
Acetylation-dependent ADP-ribosylation by Trypanosoma brucei Sir2
J. Biol. Chem., February 29, 2008; 283(9): 5317 - 5326.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. C. Smith and J. M. Denu
Acetyl-lysine Analog Peptides as Mechanistic Probes of Protein Deacetylases
J. Biol. Chem., December 21, 2007; 282(51): 37256 - 37265.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. Ono, A. Kasamatsu, S. Oka, and J. Moss
The 39-kDa poly(ADP-ribose) glycohydrolase ARH3 hydrolyzes O-acetyl-ADP-ribose, a product of the Sir2 family of acetyl-histone deacetylases
PNAS, November 7, 2006; 103(45): 16687 - 16691.
[Abstract] [Full Text] [PDF]

Home page
 Microbiol. Mol. Biol. Rev.Home page
P. O. Hassa, S. S. Haenni, M. Elser, and M. O. Hottiger
Nuclear ADP-Ribosylation Reactions in Mammalian Cells: Where Are We Today and Where Are We Going?
Microbiol. Mol. Biol. Rev., September 1, 2006; 70(3): 789 - 829.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
O. Grubisha, L. A. Rafty, C. L. Takanishi, X. Xu, L. Tong, A.-L. Perraud, A. M. Scharenberg, and J. M. Denu
Metabolite of SIR2 Reaction Modulates TRPM2 Ion Channel
J. Biol. Chem., May 19, 2006; 281(20): 14057 - 14065.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. B. Pillai, A. Isbatan, S.-i. Imai, and M. P. Gupta
Poly(ADP-ribose) Polymerase-1-dependent Cardiac Myocyte Cell Death during Heart Failure Is Mediated by NAD+ Depletion and Reduced Sir2{alpha} Deacetylase Activity
J. Biol. Chem., December 30, 2005; 280(52): 43121 - 43130.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Nemoto, M. M. Fergusson, and T. Finkel
SIRT1 Functionally Interacts with the Metabolic Regulator and Transcriptional Coactivator PGC-1{alpha}
J. Biol. Chem., April 22, 2005; 280(16): 16456 - 16460.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
C. M. Gallo, D. L. Smith Jr., and J. S. Smith
Nicotinamide Clearance by Pnc1 Directly Regulates Sir2-Mediated Silencing and Longevity
Mol. Cell. Biol., February 1, 2004; 24(3): 1301 - 1312.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. D. Jackson, M. T. Schmidt, N. J. Oppenheimer, and J. M. Denu
Mechanism of Nicotinamide Inhibition and Transglycosidation by Sir2 Histone/Protein Deacetylases
J. Biol. Chem., December 19, 2003; 278(51): 50985 - 50998.
[Abstract] [Full Text] [PDF]

Home page
 Microbiol. Mol. Biol. Rev.Home page
K. J. Bitterman, O. Medvedik, and D. A. Sinclair
Longevity Regulation in Saccharomyces cerevisiae: Linking Metabolism, Genome Stability, and Heterochromatin
Microbiol. Mol. Biol. Rev., September 1, 2003; 67(3): 376 - 399.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
S. C. Dryden, F. A. Nahhas, J. E. Nowak, A.-S. Goustin, and M. A. Tainsky
Role for Human SIRT2 NAD-Dependent Deacetylase Activity in Control of Mitotic Exit in the Cell Cycle
Mol. Cell. Biol., May 1, 2003; 23(9): 3173 - 3185.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. A. Rafty, M. T. Schmidt, A.-L. Perraud, A. M. Scharenberg, and J. M. Denu
Analysis of O-Acetyl-ADP-ribose as a Target for Nudix ADP-ribose Hydrolases
J. Biol. Chem., November 27, 2002; 277(49): 47114 - 47122.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. J. Bitterman, R. M. Anderson, H. Y. Cohen, M. Latorre-Esteves, and D. A. Sinclair
Inhibition of Silencing and Accelerated Aging by Nicotinamide, a Putative Negative Regulator of Yeast Sir2 and Human SIRT1
J. Biol. Chem., November 15, 2002; 277(47): 45099 - 45107.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
S. N. Garcia and L. Pillus
A Unique Class of Conditional sir2 Mutants Displays Distinct Silencing Defects in Saccharomyces cerevisiae
Genetics, October 1, 2002; 162(2): 721 - 736.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J.-H. Chang, H.-C. Kim, K.-Y. Hwang, J.-W. Lee, S. P. Jackson, S. D. Bell, and Y. Cho
Structural Basis for the NAD-dependent Deacetylase Mechanism of Sir2
J. Biol. Chem., September 6, 2002; 277(37): 34489 - 34498.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
B. Schwer, B. J. North, R. A. Frye, M. Ott, and E. Verdin
The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase
J. Cell Biol., August 19, 2002; 158(4): 647 - 657.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.