Identification and functional characterization of a novel bipartite nuclear localization sequence in ARID1A

Nicholas W Bateman; Yutaka Shoji; Kelly A Conrads; Kevin D Stroop; Chad A Hamilton; Kathleen M Darcy; George L Maxwell; John I Risinger; Thomas P Conrads

doi:10.1016/j.bbrc.2015.11.080

Identification and functional characterization of a novel bipartite nuclear localization sequence in ARID1A

Biochem Biophys Res Commun. 2016 Jan 1;469(1):114-119. doi: 10.1016/j.bbrc.2015.11.080. Epub 2015 Nov 22.

Authors

Nicholas W Bateman¹, Yutaka Shoji², Kelly A Conrads³, Kevin D Stroop³, Chad A Hamilton⁴, Kathleen M Darcy¹, George L Maxwell⁵, John I Risinger², Thomas P Conrads⁶

Affiliations

¹ 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.
² Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids 49503, MI, USA.
³ Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale 22003, VA, USA.
⁴ 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.
⁵ Department of Obstetrics and Gynecology, Inova Fairfax Hospital, Falls Church, VA 22042, USA.
⁶ 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.

PMID: 26614907
DOI: 10.1016/j.bbrc.2015.11.080

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.

Keywords: ARID1A; Nuclear localization sequence; Trafficking; Tumor suppressor.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Amino Acid Sequence
Cell Nucleus / chemistry*
Cell Nucleus / metabolism*
DNA-Binding Proteins
Molecular Sequence Data
Mutagenesis, Site-Directed
Nuclear Localization Signals / chemistry*
Nuclear Localization Signals / metabolism*
Nuclear Proteins / chemistry*
Nuclear Proteins / metabolism*
Transcription Factors / chemistry*
Transcription Factors / metabolism*

Substances

ARID1A protein, human
DNA-Binding Proteins
Nuclear Localization Signals
Nuclear Proteins
Transcription Factors