Take our Survey

Reference: Beauharnois JM, et al. (2013) Sirtuin 6: a review of biological effects and potential therapeutic properties. Mol Biosyst 9(7):1789-806

Reference Help

Abstract


Sirtuins, possessing either histone deacetylase or mono-ribosyltransferase activity, regulate important pathways in bacteria, archaea and eukaryotes. SIRT6, an enzyme highly expressed in skeletal muscles, brain, heart, liver, and thymus, affects transcriptional regulation in a tissue-specific manner. This enzyme has a two-domain structure that consists of a large Rossmann fold and a smaller and structurally more varied sequence containing a Zn(2+)-binding motif. The C-terminus is required for proper nuclear localization, while the N-terminus is important for chromatin association and for intrinsic catalytic activity. SIRT6 promotes resistance to DNA damage and oxidative stress, the principal defects associated with age-related diseases. The modulation of aging and other metabolic functions by SIRT6 may be indicative of previously unrecognized regulatory systems in the cell. The propensity of individual SIRT6 molecules to undergo intramolecular mono-ADP-ribosylation, suggests this auto-ribosylation may contribute to the self-regulation of SIRT6 function. Until recently, SIRT6 was an orphan enzyme whose catalytic activity and substrates were unclear. It was known that, similar to the yeast Sir2 protein, human SIRT6 deacetylates histones and regulates DNA stability and repair; however, new mechanistic insights can be derived from the discovery of the highly substrate-specific histone deacetylase activity of SIRT6. This deacetylase activity promotes proper chromatin function in several physiologic contexts, to include telomere and genome stabilization, gene expression and DNA repair. By maintaining both the integrity and the expression of the mammalian genome, SIRT6 may help prevent cellular senescence. Moreover, successful molecular modulation of SIRT6 activity may lead to the development of new chemotherapeutic modalities. The action of SIRT6 is described in this review, with an emphasis on the cellular roles of the enzyme and the relation of those enzymatic functions to human biology and disease.

Reference Type
Journal Article
Authors
Beauharnois JM, Bolivar BE, Welch JT
Primary Lit For
Additional Lit For
Review For

Interaction Annotations


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Type Assay Annotation Action Modification Phenotype Source Reference

Gene Ontology Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Gene Ontology Term Qualifier Aspect Method Evidence Source Assigned On Annotation Extension Reference

Phenotype Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.

Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Regulation Annotations


Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, SPELL, or YeastMine.

Regulator Target Experiment Assay Construct Conditions Strain Background Reference