The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Mouse Sir2 Homolog SIRT6 Is a Nuclear ADP-ribosyltransferase
Open accessAbstract
Members of the Sir2 family of NAD-dependent protein deacetylases regulate diverse cellular processes including aging, gene silencing, and cellular differentiation. Here, we report that the distant mammalian Sir2 homolog SIRT6 is a broadly expressed, predominantly nuclear protein. Northern analysis of embryonic samples and multiple adult tissues revealed mouse SIRT6 (mSIRT6) mRNA peaks at day E11, persisting into adulthood in all eight tissues examined. At the protein level, mSIRT6 was readily detectable in the same eight tissue types, with the highest levels in muscle, brain, and heart. Subcellular localization studies using both C- and N-terminal green fluorescent protein fusion proteins showed mSIRT6-green fluorescent protein to be a predominantly nuclear protein. Indirect immunofluorescence using antibodies to two different mSIRT6 epitopes confirmed that endogenous mSIRT6 is also largely nuclear. Consistent with previous findings, we did not observe any NAD+-dependent protein deacetylase activity in preparations of mSIRT6. However, purified recombinant mSIRT6 did catalyze the robust transfer of radiolabel from [32P]NAD to mSIRT6. Two highly conserved residues within the catalytic core of the protein were required for this reaction. This reaction is most likely mono-ADP-ribosylation because only the modified form of the protein was recognized by an antibody specific to mono-ADP-ribose. Surprisingly, we observed that the catalytic mechanism of this reaction is intra-molecular, with individual molecules of mSIRT6 directing their own modification. These results provide the first characterization of a Sir2 protein from phylogenetic class IV.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“SIRT6 has multiple biochemical activities, including protein deacetylation22 and mono-ADP ribosylation19,29.”
From SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age (2014) · cites this paper as [29]
In the citing paper
“SIRT4 and SIRT6 also function as ADP-ribosyltransferases, indicating that sirtuins contribute to cell regulation also through mechanisms beyond modulation of protein acetylation, which require further investigation17,18.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [18]
Citations
Cites
Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
Imai, S.-I., Armstrong, C. M., Kaeberlein, M., & Guarente, L. (2000) · Nature · doi:10.1038/35001622 · Cited by 3,510
Self-citationStress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
Brunet, A., Sweeney, L. B., Sturgill, J. F., Chua, K. F., Greer, P. L., Lin, Y., Tran, H., Ross, S. E., Mostoslavsky, R., Cohen, H. Y., et al. (2004) · Science · doi:10.1126/science.1094637 · Cited by 3,239
Kaeberlein, M., McVey, M., & Guarente, L. (1999) · Genes & Development · doi:10.1101/gad.13.19.2570 · Cited by 2,253
Self-citationSirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ
Picard, F., Kurtev, M. V., Chung, N., Topark‐Ngarm, A., Senawong, T., de Oliveira, R. M., Leid, M. E., McBurney, M. W., & Guarente, L. (2004) · Nature · doi:10.1038/nature02583 · Cited by 1,943
Self-citationSirtuin activators mimic caloric restriction and delay ageing in metazoans
Wood, J. G., Rogina, B., Lavu, S., Howitz, K., Helfand, S. L., Tatar, M., & Sinclair, D. (2004) · Nature · doi:10.1038/nature02789 · Cited by 1,868
Lin, S.-J., Defossez, P.-A., & Guarente, L. (2000) · Science · doi:10.1126/science.289.5487.2126 · Cited by 1,775
Self-citationIncreased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans
Tissenbaum, H. A., & Guarente, L. (2001) · Nature · doi:10.1038/35065638 · Cited by 1,603
Self-citationThe Human Sir2 Ortholog, SIRT2, Is an NAD+-Dependent Tubulin Deacetylase
North, B. J., Marshall, B. L., Borra, M. T., Denu, J. M., & Verdin, E. M. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00038-8 · Cited by 1,542
The Sir2 Family of Protein Deacetylases
Blander, G., & Guarente, L. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.073651 · Cited by 1,497
Self-citationPhylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins
Frye, R. A. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3000 · Cited by 1,409
Flagged first, then by citations
Research works printed but not linked: 1
- Kain, 1994, BioTechniques, 17, 982
Cited by
Sorted by citations
Reactive oxygen species, cellular redox systems, and apoptosis
Circu, M. L., & Aw, T. Y. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.12.022 · Cited by 3,340
Mammalian Sirtuins: Biological Insights and Disease Relevance
Haigis, M. C., & Sinclair, D. A. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathol.4.110807.092250 · Cited by 2,085
Sirtuins as regulators of metabolism and healthspan
Houtkooper, R. H., Pirinen, E., & Auwerx, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3293 · Cited by 2,008
Sirtuins in mammals: insights into their biological function
Michán, S., & Sinclair, D. A. (2007) · Biochemical Journal · doi:10.1042/bj20070140 · Cited by 1,750
Cantó, C., Menzies, K. J., & Auwerx, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.023 · Cited by 1,648
Metadata
- Authors
- Liszt, G., Ford, E., Kurtev, M., & Guarente, L.
- Affiliations
- Massachusetts Institute of Technology (US)
- Corresponding author
- Guarente, Leonard
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-06
- Volume
- 280
- Issue
- 22
- Pages
- 21313-21320
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2044836637
- Cited by
- 548
- References
- 31
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 12 · 2023: 20 · 2022: 24 · 2021: 35 · 2020: 30 · 2019: 26 · 2018: 34 · 2017: 25 · 2016: 34 · 2015: 35 · 2014: 23 · 2013: 43 · 2012: 30
- FWCI
- 12.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- SIRT6, ADP-ribosyltransferase, mono-ADP-ribosylation, NAD+-dependent deacetylase, nuclear localization, tissue expression, embryonic development, catalytic mechanism
- MeSH terms
- Actins, Adenosine Diphosphate, Adenosine Diphosphate Ribose, Amino Acid Sequence, Animals, Epitopes, Catalysis, Cell Nucleus, Cytoplasm, Dose-Response Relationship, Drug, Microscopy, Fluorescence, Molecular Sequence Data, Phylogeny, Plasmids, Recombinant Fusion Proteins, Recombinant Proteins, Ribose, RNA, RNA, Messenger, Serine, Time Factors, Tissue Distribution, Blotting, Northern, Blotting, Western, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Fluorescent Antibody Technique, Indirect, Catalytic Domain, Gene Silencing, ADP Ribose Transferases, Sirtuins, NIH 3T3 Cells, Green Fluorescent Proteins, Mice, Sirtuin 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
