1 H, 13 C, and 15 N backbone assignments of the C-terminal region of the human retinoic acid-induced protein 2
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ARTICLE
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H, 13C, and 15N backbone assignments of the C-terminal region of the human retinoic acid-induced protein 2 Andras Lang1 · Nishit Goradia2 · Harriet Wikman3 · Stefan Werner3 · Matthias Wilmanns2,4 · Oliver Ohlenschläger1 Received: 25 March 2020 / Accepted: 10 June 2020 © Springer Nature B.V. 2020
Abstract Retinoic acid-induced protein 2 is a human protein of 530 residues encoded by the RAI2 gene (Q9Y5P3; RAI2_HUMAN). RAI2 is a novel tumor suppressor protein whose depletion in breast cancer cell lines results in the downregulation of several genes associated with differentiation along with increased invasiveness and aggressive tumor phenotype of the cells. The role of the protein is specified to be a transcriptional regulator that promotes chromosomal stability and hence controls the expression of several regulators of cancer and metastasis. Structurally, RAI2 remains an unknown entity and, hence, to obtain a detailed view on the structure function relationship we report the 1H, 13C, and 15N resonance assignments for the backbone and side chain nuclei of the C-terminal region (a.a. 303–451 of UniProt Q9Y5P3) of RAI2. Keywords Resonance assignments · Chemical shift · Heteronuclear NMR · Retinoic acid-induced protein 2 · Tumor suppressor
Biological context RAI2 was identified as a single-exon human gene mapped to the Xp22 region of the X-chromosome. This 530-amino acid protein possesses 94% homology to the corresponding mouse retinoic acid-induced gene product and is present in the majority of fetal as well as adult tissues. The protein comprises of a 68 amino acids long proline-rich domain similar to the one present in p53 tumor suppressor protein. It plays an important role in modulation of gene expression and maintaining cellular differentiation during embryonal development (Walpole et al. 1999). Andras Lang and Nishit Goradia contributed equally to this work. * Oliver Ohlenschläger oliver.ohlenschlaeger@leibniz‑fli.de 1
Leibniz Institute on Aging – Fritz Lipmann Institute, Beutenbergstr. 11, 07745 Jena, Germany
European Molecular Biology Laboratory, Hamburg Unit, Notkestrasse 85, 22607 Hamburg, Germany
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Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany
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University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany
It was almost 15 years later, Werner et al. identified RAI2 as a novel genetic determinant associated with early metastatic spread of hormone receptor positive breast tumors. Interestingly, RAI2 depletion leads to the loss of differentiation-sustaining transcription factors and induces morphologic changes consistent with the epithelial to mesenchymal transition and acquisition of aggressive and invasive phenotype (Werner et al. 2015). This potential tumor suppressor role of RAI2 makes it attractive for functional and structural characterization. As a first step to characterize the protein and its interactions, the truncated RAI2 protein (RAI2303–451) was recombinantly generated for
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