Identification of Novel Interacting Partners of Sirtuin6

Abstract

SIRT6 is a member of the Sirtuin family of histone deacetylases that has been implicated in inflammatory, aging and metabolic pathways. Some of its actions have been suggested to be via physical interaction with NFκB and HIF1α and transcriptional regulation through its histone deacetylase activity. Our previous studies have investigated the histone deacetylase activity of SIRT6 and explored its ability to regulate the transcriptional responses to an inflammatory stimulus such as TNFα. In order to develop a greater understanding of SIRT6 function we have sought to identify SIRT6 interacting proteins by both yeast-2-hybrid and co-immunoprecipitation studies. We report a number of interacting partners which strengthen previous findings that SIRT6 functions in base excision repair (BER), and novel interactors which suggest a role in nucleosome and chromatin remodeling, the cell cycle and NFκB biology.

A Proteomic Perspective of Sirtuin 6 (SIRT6) Phosphorylation and Interactions and Their Dependence on Its Catalytic Activity

“…PARP1 and C-terminal binding protein interacting protein). We also detected the recently reported MYBBP1A (known RelA/p65 interactor) and SMARCA5 (linked to chromatin remodeling) SIRT6 associations (38); however, these interactions did not pass our specificity criteria and were excluded from the final network.…”

“…This has revealed the C-terminal binding protein interacting protein, involved in double-strand DNA break repair, and poly-[ADP-ribose] polymerase 1 (PARP1) as SIRT6 non-histone substrates. Other known interactions include DNA-PKcs (35), RelA/p65, and TDG, TSPYL2, and PIAS1 (38), suggesting SIRT6 functions in DNA repair, cell cycle regulation, and NF-kB transcription. However, further knowledge of SIRT6 protein associations and/or substrates is required in order for SIRT6 functions to be explored and relevant molecular mechanisms and regulatory factors to be characterized.…”

Upregulation of SIRT6 predicts poor prognosis and promotes metastasis of non-small cell lung cancer via the ERK1/2/MMP9 pathway

“…SIRT6 is highly expressed in thymus, skeletal, brain and muscle tissues [24, 25]. SIRT6 has two major biochemical activities, functioning as (1) a deacetylase and (2) a mono-ADP ribosyltransferase [26, 27]. SIRT6 participates in numerous biological processes, including maintaining genomic stability, modulating senescence and development of age-related diseases [8, 9].…”

Genetic Deletion of Cell Division Autoantigen 1 Retards Diabetes-Associated Renal Injury

“…27 Recent studies have identified direct binding of CDA1 by its N terminus to SIRT6 (Sirtuin 6), a histone deacetylase known to be involved in inflammatory signaling and cell cycle regulation. 28 Indeed, recent studies have shown that SIRT6 overexpression is able to antagonize TGF-b-mediated senescence in human bronchial epithelial cells. 29 The mechanism by which CDA1 deletion attenuates TGF-b signaling in the kidney is a matter of ongoing investigation.…”