Fluorescence in situ hybridization and chromosomal organization of the human Sirtuin 7 gene

ArticleinInternational Journal of Oncology 28(4):899-908 · May 2006with7 Reads
DOI: 10.3892/ijo.28.4.899 · Source: PubMed
Abstract
Sirtuin 7 (SIRT7) is a member of the sirtuin family of protein deacetylases and is, therefore, a derivative of yeast Silent information regulator 2 (SIR2). SIR2 and its mammalian orthologs play an important role in epigenetic gene silencing, DNA recombination, cellular differentiation and metabolism, and the regulation of aging. In contrast to most sirtuins, SIRT7 does not exert characteristic NAD+-dependent deacetylase activity. We have isolated and characterized the human Sirt7 genomic sequence, which spans a region of 6.2 kb and which has one single genomic locus. Determination of the exon/intron splice junctions found the full-length SIRT7 protein to consist of 10 exons ranging in size from 71 bp (exon 4) to 237 bp (exon 7). The human Sirt7 open reading frame encodes a 400-aa protein with a predictive molecular weight of 44.9 kDa and an isoelectric point of 9.80. Characterization of the 5' flanking genomic region, which precedes the Sirt7 open reading frame, revealed a TATA- and CCAAT-box less promoter that lacks CpG islands. A number of AML-1 and GATA-x transcription factor binding sites were found, which remain to be further evaluated experimentally. Fluorescence in situ hybridization analysis localized the human Sirt7 gene to chromosome 17q25.3; a region which is frequently affected by chromosomal alterations in acute leukemias and lymphomas. Human SIRT7 appears to be most predominantly expressed in the blood and in CD33+ myeloid bone marrow precursor cells, while the lowest levels are found in the ovaries and skeletal muscle. Functional characteristics of SIRT7 are essentially unknown at present and remain to be further elucidated.
    • "It is located on chromosome 17q25.3; a region frequently associated with chromosomal alterations in leukemias and lymphomas [29]. SIRT7 is also upregulated in breast and thyroid cancers [30,31,32]. "
    [Show abstract] [Hide abstract] ABSTRACT: Sirtuins (SIRT1-7), the mammalian homologues of the Sir2 gene in yeast, have emerging roles in age-related diseases, such as cardiac hypertrophy, diabetes, obesity, and cancer. However, the role of several sirtuin family members, including SIRT1 and SIRT3, in cancer has been controversial. The aim of this review is to explore and discuss the seemingly dichotomous role of SIRT3 in cancer biology with particular emphasis on its potential role as a tumor promoter and tumor suppressor. This review will also discuss the potential role of SIRT3 as a novel therapeutic target to treat cancer.
    Full-text · Article · Aug 2011
    • "In fact, it has been shown that transcription of rRNA directly depends on SIRT7 content (Ford et al., 2006; Mostoslavsky et al., 2006), with the highest SIRT7 level found in blood and CD33+ myeloid bone marrow precursor cells. On the other hand, lower SIRT7 levels were observed in ovaries and mammalian skeletal muscle (Voelter-Mahlknecht et al., 2006). In case of SIRT7 ablation, cells do not proliferate and enter the apoptotic pathway (Ford et al., 2006), as opposed to an increased SIRT7 level, which has been associated with carcinogenesis. "
    [Show abstract] [Hide abstract] ABSTRACT: The link between sirtuin activity and mitochondrial biology has recently emerged as an important field. This conserved family of NAD(+)-dependent deacetylase proteins has been described to be particularly involved in metabolism and longevity. Recent studies on protein acetylation have uncovered a high number of acetylated mitochondrial proteins indicating that acetylation/deacetylation processes may be important not only for the regulation of mitochondrial homeostasis but also for metabolic dysfunction in the context of various diseases such as metabolic syndrome/diabetes and cancer. The functional involvement of sirtuins as sensors of the redox/nutritional state of mitochondria and their role in mitochondrial protection against stress are hereby described, suggesting that pharmacological manipulation of sirtuins is a viable strategy against several pathologies.
    Full-text · Article · Jul 2011
    • "The protein SIRT7 localizes to the nucleolus of human cells (Ford et al. 2006; Michishita et al. 2005; Voelter-Mahlknecht et al. 2006a). So far, neither a deacetylase nor an ADP ribosyltransferase activity has been detected for SIRT7. "
    [Show abstract] [Hide abstract] ABSTRACT: Aging is the natural trace that time leaves behind on life during blossom and maturation, culminating in senescence and death. This process is accompanied by a decline in the healthy function of multiple organ systems, leading to increased incidence and mortality from diseases such as diabetes, cancer, cardiovascular disease, and neurodegeneration. Based on the fact that both sirtuin expression and activity appear to be upregulated in some types of cancer while they are being downregulated in others, there is quite some controversy stirring up as to the role of sirtuins, acting as cancer suppressors in some cases while under other circumstances they may promote cellular malignancy. It is therefore currently quite unclear as to what extent and under which particular circumstances sirtuin activators and/or inhibitors will find their place in the treatment of age-related disease and cancer. In this review, we take an effort to bring together the highlights of sirtuin research in order to shed some light on the mechanistic impact that sirtuins have on the pathogenesis of cellular malignancy.
    Article · Dec 2010
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