title: Proteomic analysis of the SIRT6 interactome: novel links to genome maintenance and cellular stress signaling.
abstract: The chromatin regulatory factor SIRT6 plays pivotal roles in metabolism, tumor suppression, and aging biology. Despite the fundamental roles of SIRT6 in physiology and disease, only a handful of molecular and functional interactions of SIRT6 have been reported. Here, we characterize the SIRT6 interactome and identify 80+ novel SIRT6-interacting proteins. The discovery of these SIRT6-associations considerably expands knowledge of the SIRT6 interaction network, and suggests previously unknown functional interactions of SIRT6 in fundamental cellular processes. These include chromatin remodeling, mitotic chromosome segregation, protein homeostasis, and transcriptional elongation. Extended analysis of the SIRT6 interaction with G3BP1, a master stress response factor, uncovers an unexpected role and mechanism of SIRT6 in regulating stress granule assembly and cellular stress resistance.
authors.affiliation: 1] Department of Medicine, Division of Endocrinology, Gerontology and Metabolism, School of Medicine, Stanford University, Stanford, California 94305, USA [2] Geriatric Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, California 94304, USA.
authors.forename: Federica
authors.initials: F
authors.lastname: Simeoni
authors.forename: Luisa
authors.initials: L
authors.lastname: Tasselli
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.forename: Lidia
authors.initials: L
authors.lastname: Villanova
authors.forename: Mayumi
authors.initials: M
authors.lastname: Hayashi
authors.forename: Kazuishi
authors.initials: K
authors.lastname: Kubota
authors.forename: Fujio
authors.initials: F
authors.lastname: Isono
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Garcia
authors.forename: Eriko
authors.initials: E
authors.lastname: Michishita-Kioi
authors.forename: Katrin F
authors.initials: KF
authors.lastname: Chua
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D004265:DNA Helicases; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D000075223:Poly-ADP-Ribose Binding Proteins; D011485:Protein Binding; D060066:Protein Interaction Maps; D040901:Proteomics; D020365:RNA Helicases; D034622:RNA Interference; D000067776:RNA Recognition Motif Proteins; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000235:genetics*; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics
chemical_list: C486562:CAPRIN1 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D034741:RNA, Small Interfering; C431363:USP10 protein, human; D043222:Ubiquitin Thiolesterase; C516592:SIRT6 protein, human; D037761:Sirtuins; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases