Sjögren syndrome/scleroderma autoantigen 1 is a direct Tankyrase binding partner in cancer cells.

Harmonie Perdreau-Dahl, Cinzia Progida, Stefan J Barfeld, Hanne Guldsten, Bernd Thiede, Magnus Arntzen, Oddmund Bakke, Ian G Mills, Stefan Krauss, J Preben Morth

Journal: Communications biology 2021;3(1):123

PMID: 32170109

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Abstract

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.

Address: Membrane Transport Group, Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo, P.O. Box 1137 Blindern, 0318, Oslo, Norway.; Institute for Experimental Medical Research (IEMR), Oslo University Hospital, Ullevål PB 4956 Nydalen, NO-0424, Oslo, Norway.; Centre for Immune Regulation, Department of Molecular Biosciences, University of Oslo, Blindernveien 31, 0371, Oslo, Norway.; Prostate Cancer Group, Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo, P.O. Box 1137 Blindern, 0318, Oslo, Norway.; Department of Biosciences, University of Oslo, P.O. Box 1137 Blindern, 0316, Oslo, Norway.; Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, P.O. Box 5003, N-1432, Ås, Norway.; Patrick G Johnston Centre for Cancer Research, Queens University Belfast, Belfast, UK.; Nuffield Department of Surgical Sciences, Faculty of Medical Science, University of Oxford, John Radcliffe Hospital, Oxford, UK.; Department of Immunology and Transfusion Medicine, Oslo University Hospital, and Hybrid Technology Hub-Centre of Excellence, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.; Membrane Transport Group, Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo, P.O. Box 1137 Blindern, 0318, Oslo, Norway. [email protected].; Institute for Experimental Medical Research (IEMR), Oslo University Hospital, Ullevål PB 4956 Nydalen, NO-0424, Oslo, Norway. [email protected].; Enzyme and Protein Chemistry, Section for Protein Chemistry and Enzyme Technology, Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads, 2800, Kgs. Lyngby, Denmark. [email protected].

DOI: 10.1038/s42003-020-0851-2

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MeSH Terms: Active Transport, Cell Nucleus, Autoantigens, Binding Sites, Crystallography, X-Ray, HeLa Cells, Humans, Neoplasms, Nuclear Export Signals, Phylogeny, Protein Binding, Protein Conformation, alpha-Helical, Protein Domains, Protein Interaction Maps, Ribonucleoproteins, Tankyrases, Transfection