Identification of two novel isoforms of mouse NUR77 lacking N‐terminal domains

Abstract

Nur77 is a member of nuclear receptor superfamily that acts as a transcription factor and regulates expression of multiple genes. Subcellular localization of Nur77 protein plays an important role in the survival and cell death. In this study, we have predicted and confirmed alternatively spliced two new transcripts of Nur77 gene in mouse. The newly identified transcripts have their alternatively spliced first exon located upstream of published 5'-UTR of the gene. Transcription factor binding sites in the possible promoter regions of these transcripts were also analyzed. Expression of novel transcript variants was found to be significantly lower than the already published transcript. New transcript variants encode for NUR77 protein isoforms which are significantly smaller in size due to lack of transactivation domain and a part of DNA binding domain. Western blot analysis using NUR77 specific antibody confirmed the existence of these smaller variants in mouse. Localization of these new isoforms was predicted to be majorly outside the nucleus. In silico analysis of the conceptually translated proteins was performed using different bioinformatics tools. The results obtained in this study offer further insight into novel area of research on extensively studied Nur77. © 2017 IUBMB Life, 69(2):106-114, 2017.

Characteristics of Nur77 and its ligands as potential anticancer compounds (Review)

“…1B ) ( 18 ). Rehman et al ( 19 ) identified two protein subtypes in mice that lack the Nur77 N-terminal domain, and the localization of these isoforms was predicted to be predominantly outside the nucleus. Therefore, N-terminal transactivation domain may be required for the transport of Nur77 from the nucleus to the cytoplasm.…”

Cell-Type Specific Profiling of Histone Post-Translational Modifications in the Adult Mouse Striatum

“…Interestingly, H3K4me3 was also enriched at several Nr4a1 exons suggesting alternative transcription start sites 73 . We posit that activation of Nr4a1 at alternative promoters may produce Nr4a1 isoforms that lack the N-terminal transactivation domain, which has important implications on downstream target gene activation 74 . In addition, cell-type specific H3K27me3 depletion at Cartpt could establish the mechanism that confers A2a specific expression of this peptide.…”

International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily—Update 2023

“…The NR4A1 gene is located on chromosome 12 in humans, which encodes for a 598-residue protein (Hazel, Nathans, & Lau, 1988). It is hypothesized that the NTD permits NRFI-B translocation from the nucleus to the cytoplasm (Rehman, Sarwar, Husain, Ishqi, & Tabish, 2017). The DBD recognizes specific NGFI-B response elements (NBRE; AAAGGTCA) as a monomer and binds Nur-response elements (NurRE; TGATATTTN 6 AAATGCCA; N is any nucleotide) as a homodimer or heterodimer with either NURR1 or NOR-1.…”