title: Identification and functional characterization of a novel bipartite nuclear localization sequence in ARID1A.
abstract: AT-rich interactive domain-containing protein 1A (ARID1A) is a recently identified nuclear tumor suppressor frequently altered in solid tumor malignancies. We have identified a bipartite-like nuclear localization sequence (NLS) that contributes to nuclear import of ARID1A not previously described. We functionally confirm activity using GFP constructs fused with wild-type or mutant NLS sequences. We further show that cyto-nuclear localized, bipartite NLS mutant ARID1A exhibits greater stability than nuclear-localized, wild-type ARID1A. Identification of this undescribed functional NLS within ARID1A contributes vital insights to rationalize the impact of ARID1A missense mutations observed in patient tumors.
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale 22003, VA, USA; The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda 20889, MD, USA.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Bateman
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids 49503, MI, USA.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shoji
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale 22003, VA, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Conrads
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale 22003, VA, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Stroop
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale 22003, VA, USA; The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda 20889, MD, USA; Gynecologic Oncology Service, Department of Obstetrics and Gynecology, Walter Reed National Military Medical Center, 8901 Wisconsin Ave, MD, Bethesda, 20889, USA; Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda 20814, MD, USA.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Hamilton
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale 22003, VA, USA; The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda 20889, MD, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Darcy
authors.affiliation: Department of Obstetrics and Gynecology, Inova Fairfax Hospital, Falls Church, VA 22042, USA.
authors.forename: George L
authors.initials: GL
authors.lastname: Maxwell
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids 49503, MI, USA.
authors.forename: John I
authors.initials: JI
authors.lastname: Risinger
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale 22003, VA, USA; The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda 20889, MD, USA; Gynecologic Oncology Service, Department of Obstetrics and Gynecology, Walter Reed National Military Medical Center, 8901 Wisconsin Ave, MD, Bethesda, 20889, USA. Electronic address: conrads@whirc.org.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Conrads
mesh_terms: D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000737:chemistry* / Q000378:metabolism*; D004268:DNA-Binding Proteins; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D019913:Nuclear Localization Signals / Q000737:chemistry* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*
chemical_list: C112476:ARID1A protein, human; D004268:DNA-Binding Proteins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D014157:Transcription Factors
keywords: ARID1A; Nuclear localization sequence; Trafficking; Tumor suppressor