Journal
BIOMOLECULAR NMR ASSIGNMENTS
Volume 17, Issue 1, Pages 37-41Publisher
SPRINGER
DOI: 10.1007/s12104-022-10117-z
Keywords
RBP (RNA binding protein); hnRNP A18 (heterogeneous ribonucleoprotein A18); CIRBP (cold inducible RNA binding protein); IDD (intrinsically disordered domain)
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hnRNP A18 is an RNA binding protein involved in the hypoxic cellular stress response and regulation of CTLA-4 expression. Phosphorylation of hnRNP A18 by CK2 and GSK-3 beta results in its translocation to the cytosol and interaction with pro-survival mRNA transcripts. This study provides the backbone and sidechain resonances of hnRNP A18, serving as a foundation for future drug discovery studies and the investigation of structural changes upon phosphorylation.
Heterogeneous ribonuclear protein A18 (hnRNP A18) is an RNA binding protein (RBP) involved in the hypoxic cellular stress response and regulation of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression in melanoma, breast cancer, prostate cancer, and colon cancer solid tumors. hnRNP A18 is comprised of an N-terminal structured RNA recognition motif (RMM) and a C-terminal intrinsically disordered domain (IDD). Upon cellar stressors, such as UV and hypoxia, hnRNP A18 is phosphorylated by casein kinase 2 (CK2) and glycogen synthase kinase 3 beta (GSK-3 beta). After phosphorylation, hnRNP A18 translocates from the nucleus to the cytosol where it interacts with pro-survival mRNA transcripts for proteins such as hypoxia inducible factor 1 alpha and CTLA-4. Both the hypoxic cellular response and modulation of immune checkpoints by cancer cells promote chemoradiation resistance and metastasis. In this study, the (1) H, (13) C, and (15) N backbone and sidechain resonances of the 172 amino acid hnRNP A18 were assigned sequence-specifically and provide a framework for future NMR-based drug discovery studies toward targeting hnRNP A18. These data will also enable the investigation of the dynamic structural changes within the IDD of hnRNP A18 upon phosphorylation by CK2 and GSK-3 beta to provide critical insight into the structure and function of IDDs.
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