The Sir2 protein family: A novel deacetylase for gene silencing and more

Shore, David

doi:10.1073/pnas.011506198

Cited by 72 publications

(49 citation statements)

References 20 publications

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“…The silent information regulator 2 (Sir2) is reported to be a nicotinamide adenine dinucleotide (NAD)-dependent histonedeacetylase (Langley et al, 2002). In the budding yeast Saccharomyces cerevisiae, Sir2 is required for silencing in mating type genes, telomeres, and ribosomal DNA (Shore, 2000), and promotes longevity (Guarente, 2000(Guarente, , 2001Sinclair, 2002). The mammalian Sirtuin SIRT1 gene product encodes an NAD-dependent nuclear HDAC that is the closest structural ortholog of the yeast Sir2 protein (Frye, 2000).…”

Section: Discussionmentioning

confidence: 99%

SIRT1 interacts with p73 and suppresses p73‐dependent transcriptional activity

Dai

Wang

Sun

et al. 2006

Journal Cellular Physiology

124

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The tumor suppressor p53-related p73 shares significant amino-acid sequence identity with p53. Like p53, p73 recognizes canonical p53 DNA-binding sites and activates p53-responsive target genes and induces apoptosis. Moreover, SIRT1 binds to p53 while repressing the expression of their target genes. Here, we report that SIRT1 also binds to p73 and suppresses p73-dependent transcriptional activity. SIRT1 in human cells reduces the transcriptional activity of p73, and partly inhibits apoptosis induced by p73. Furthermore, SIRT1 can deacetylate p73 protein acetylation both in vivo and in vitro. Collectively, these data suggest that SIRT1 can modulate p73 activity via deacetylation.

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Section: Discussionmentioning

confidence: 99%

SIRT1 interacts with p73 and suppresses p73‐dependent transcriptional activity

Dai

Wang

Sun

et al. 2006

Journal Cellular Physiology

124

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“…The enzymatic activity of Sir2 proteins is mainly exerted by its core domain containing 260 amino acids that is conserved among Sir2 family genes (Sherman et al, 1999), and mutations of the conserved residues within this globular core domain leads to a loss of deacetylase acivity (Frye, 1999;Sherman et al, 1999;Tanny et al, 1999). At least three of the SIR proteins in yeast, Sir2, 3 and 4, participate in gene silencing, as well as in proper cell cycle progression, radiation resistance and genomic stability (Brachmann et al, 1995;Shore, 2000;Gasser and Cockell, 2001).…”

Section: Introductionmentioning

confidence: 99%

SIRT1 promotes DNA repair activity and deacetylation of Ku70

Jeong

Juhn²,

Lee³

et al. 2007

Exp Mol Med

309

217

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Human SIRT1 controls various physiological responses including cell fate, stress, and aging, through deacetylation of its specific substrate protein. In processing DNA damage signaling, SIRT1 attenuates a cellular apoptotic response by deacetylation of p53 tumor suppressor. The present study shows that, upon exposure to radiation, SIRT1 could enhance DNA repair capacity and deacetylation of repair protein Ku70. Ectopically over-expressed SIRT1 resulted in the increase of repair of DNA strand breakages produced by radiation. On the other hand, repression of endogenous SIRT1 expression by SIRT1 siRNA led to the decrease of this repair activity, indicating that SIRT1 can regulate DNA repair capacity of cells with DNA strand breaks. In addition, we found that SIRT1 physically complexed with repair protein Ku70, leading to subsequent deacetylation. The dominant-negative SIRT1, a catalytically inactive form, did not induce deacetylation of Ku70 protein as well as increase of DNA repair capacity. These observations suggest that SIRT1 modulates DNA repair activity, which could be regulated by the acetylation status of repair protein Ku70 following DNA damage.

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“…Finally, the yeast SIR2 protein and its homologues form the third class. These enzymes contain nicotinamide adenine dinucleotide (NAD ϩ )-dependent activities that are insensitive to the histone deacetylase inhibitor trichostatin A (23)(24)(25).…”

mentioning

confidence: 99%

Cloning and Functional Characterization of HDAC11, a Novel Member of the Human Histone Deacetylase Family

Gao¹,

Cueto²,

Asselbergs³

et al. 2002

Journal of Biological Chemistry

650

497

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We have cloned and characterized a human cDNA that belongs to the histone deacetylase family, which we designate as HDAC11. The predicted HDAC11 amino acid sequence reveals an open reading frame of 347 residues with a corresponding molecular mass of 39 kDa. Sequence analyses of the putative HDAC11 protein indicate that it contains conserved residues in the catalytic core regions shared by both class I and II mammalian HDAC enzymes. Putative orthologues of HDAC11 exist in primate, mouse, Drosophila, and plant. Epitopetagged HDAC11 protein expressed in mammalian cells displays histone deacetylase activity in vitro. Furthermore, HDAC11's enzymatic activity is inhibited by trapoxin, a known histone deacetylase inhibitor. Multiple tissue Northern blot and real-time PCR experiments show that the high expression level of HDAC11 transcripts is limited to kidney, heart, brain, skeletal muscle, and testis. Epitope-tagged HDAC11 protein localizes predominantly to the cell nucleus. Co-immunoprecipitation experiments indicate that HDAC11 may be present in protein complexes that also contain HDAC6. These results indicate that HDAC11 is a novel and unique member of the histone deacetylase family and it may have distinct physiological roles from those of the known HDACs.In eukaryotes, DNA is packaged into chromatin structures, whose basic unit is the nucleosome. Each nucleosome consists of ϳ148 bp DNA wrapping around a core histone octamer, which includes two copies each of H2A, H2B, H3, and H4 (1). The packaging of DNA generally creates a repressive environment for gene expression; therefore, transcriptional activation of many genes requires chromatin modifications, such as the reversible acetylation of core histones. Transfer of an acetyl group from acetyl-CoA onto the ⑀-amino group of various lysine residues in the NH 2 -terminal tails of core histones is a ubiquitous process found in all eukaryotes examined. The steady state level of acetylation is controlled by the competing activities of histone acetyltransferases and histone deacetylases (HDACs).1 In general, hypoacetylated chromatin is associated with gene silencing, whereas hyperacetylation correlates with gene activation (2-5). However, recent studies have shown that histone deacetylation can also play a significant role in transcriptional activation. For example, inhibition of HDACs by trichostatin A or trapoxin both activates and silences a small fraction of cellular genes in mammalian cells (6, 7). Furthermore, mutation of the yeast histone deacetylases RPD3 and SIN3 shows that both genes are required to fully activate or to repress specific promoters (6, 8 -10). Finally, there is increasing evidence to support the idea that acetylation/deacetylation of non-histone proteins may also function in activation as well as repression of transcription (11)(12)(13)(14).Since the discovery of histone deacetylase RPD3 in Saccharomyces cerevisiae, numerous HDACs have been identified in mammalian cells, and are grouped into three classes based on sequence homologies. Members of...

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The Sir2 protein family: A novel deacetylase for gene silencing and more

Cited by 72 publications

References 20 publications

SIRT1 interacts with p73 and suppresses p73‐dependent transcriptional activity

SIRT1 interacts with p73 and suppresses p73‐dependent transcriptional activity

SIRT1 promotes DNA repair activity and deacetylation of Ku70

Cloning and Functional Characterization of HDAC11, a Novel Member of the Human Histone Deacetylase Family

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