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Sjögren syndrome/scleroderma autoantigen 1 is a direct Tankyrase binding partner in cancer cells
Communications Biology ( IF 5.9 ) Pub Date : 2020-03-13 , DOI: 10.1038/s42003-020-0851-2
Harmonie Perdreau-Dahl , Cinzia Progida , Stefan J. Barfeld , Hanne Guldsten , Bernd Thiede , Magnus Arntzen , Oddmund Bakke , Ian G. Mills , Stefan Krauss , J. Preben Morth

Sjögren syndrome/scleroderma autoantigen 1 (SSSCA1) was first described as an auto-antigen over-expressed in Sjögren’s syndrome and in scleroderma patients. SSSCA1 has been linked to mitosis and centromere association and as a potential marker candidate in diverse solid cancers. Here we characterize SSSCA1 for the first time, to our knowledge, at the molecular, structural and subcellular level. We have determined the crystal structure of a zinc finger fold, a zinc ribbon domain type 2 (ZNRD2), at 2.3 Å resolution. We show that the C-terminal domain serves a dual function as it both behaves as the interaction site to Tankyrase 1 (TNKS1) and as a nuclear export signal. We identify TNKS1 as a direct binding partner of SSSCA1, map the binding site to TNKS1 ankyrin repeat cluster 2 (ARC2) and thus define a new binding sequence. We experimentally verify and map a new nuclear export signal sequence in SSSCA1.



中文翻译:

Sjögren综合征/硬皮病自身抗原1是癌细胞中直接坦科聚合酶的结合伴侣

干燥综合征/硬皮病自身抗原1(SSSCA1)首先被描述为在干燥综合征和硬皮病患者中过表达的自身抗原。SSSCA1已与有丝分裂和着丝粒协会相关联,并作为多种实体癌的潜在标志物候选物。据我们所知,这里是我们首次在分子,结构和亚细胞水平上表征SSSCA1。我们确定了2.3分辨率下的锌指折叠(锌带状区域类型2(ZNRD2))的晶体结构。我们显示,C末端域具有双重功能,因为它既表现为Tankyrase 1(TNKS1)的相互作用位点,又表现为核输出信号。我们确定TNKS1为SSSCA1的直接结合伴侣,将结合位点映射到TNKS1锚蛋白重复簇2(ARC2),从而定义新的结合序列。

更新日期:2020-03-16
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