ARID1A中一种新型双分型核定位序列的鉴定及功能表征
Identification and functional characterization of a novel bipartite nuclear localization sequence in ARID1A.
作者信息
Bateman Nicholas W, Shoji Yutaka, Conrads Kelly A, Stroop Kevin D, Hamilton Chad A, Darcy Kathleen M, Maxwell George L, Risinger John I, Conrads Thomas P
机构信息
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.
Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids 49503, MI, USA.
出版信息
Biochem Biophys Res Commun. 2016 Jan 1;469(1):114-119. doi: 10.1016/j.bbrc.2015.11.080. Epub 2015 Nov 22.
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.
富含AT序列相互作用结构域蛋白1A（ARID1A）是一种最近发现的核肿瘤抑制因子，在实体瘤恶性肿瘤中经常发生改变。我们鉴定出一种类似双分型的核定位序列（NLS），它有助于ARID1A的核输入，此前未被描述过。我们使用与野生型或突变型NLS序列融合的GFP构建体在功能上证实了其活性。我们进一步表明，细胞核定位的双分型NLS突变型ARID1A比细胞核定位的野生型ARID1A表现出更高的稳定性。在ARID1A中鉴定出这种未被描述的功能性NLS，为理解在患者肿瘤中观察到的ARID1A错义突变的影响提供了至关重要的见解。
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