Disease relevance of CUGBP2

• These data suggest that CUGBP2 is a critical regulator of the apoptotic response to genotoxic injury in breast cancer cells [1].
• Furthermore, MCF-7 cells underwent apoptosis in response to radiation injury, which was also reversed by CUGBP2 siRNAs [1].
• We did not find BRUNOL3 mutations in 92 DiGeorge syndrome-like patients without chromosomal deletions and in 8 parents with congenital heart defect children [2].
• ETR-3 represses Tau exons 2/3 inclusion, a splicing event abnormally enhanced in myotonic dystrophy type I [3].
• Neuroblastoma apoptosis-related RNA-binding protein (NAPOR; HGMW-approved symbol CUGBP2) is a newly discovered gene prominently induced during apoptosis, suggesting that it plays a role during apoptosis [4].

High impact information on CUGBP2

• Coupled mRNA stabilization and translational silencing of cyclooxygenase-2 by a novel RNA binding protein, CUGBP2 [5].
• Antisense-mediated suppression of CUGBP2 renders radioprotection through a COX-2-dependent prostaglandin pathway, providing an in vivo demonstration of translation inhibition activity for CUGBP2 [5].
• Binding and activation by ETR-3 are directly antagonized by polypyrimidine tract binding protein (PTB) [6].
• Dynamic antagonism between ETR-3 and PTB regulates cell type-specific alternative splicing [6].
• Furthermore, CUGBP2 competitively inhibited HuR-mediated translation of the transcript [7].

Biological context of CUGBP2

• CUGBP2 plays a critical role in apoptosis of breast cancer cells in response to genotoxic injury [1].
• We have previously demonstrated that RNA binding protein CUGBP2 binds AU-rich sequences to regulate COX-2 mRNA translation [1].
• However, addition of recombinant CUGBP2 to a reconstituted system demonstrated a dose-dependent inhibition of C to U RNA editing, which was rescued with either apobec-1 or ACF [8].
• Upregulation of cardiac actin and CUGBP2 was not associated with muscle regeneration profiles, suggesting a more specific dysregulation induced by dystrophin deficiency [9].
• Using the SELEX-identified motifs to search the human genome, we identified several possible new ETR-3 targets [10].

Anatomical context of CUGBP2

• In the mouse large intestine, the editing was 48% and had a 2.7-fold relatively greater CUGBP2 level [11].
• In the human intestinal cell line Caco-2, the increase of apoB mRNA editing from approximately 1.7% to approximately 23% was associated with 6- and 3.2-fold increases of apobec-1 and CUGBP2, respectively [11].
• Short interfering RNA-mediated gene-specific knockdown of CUGBP2, GRY-RBP, and hnRNP-C1 resulted in increased editing in Caco-2 cells, consistent with their known inhibitory function [11].
• Furthermore, FLAG-tagged HuR and myc-tagged CUGBP2 colocalize in the nucleus of HCT-116 cells [7].
• Expression and mutation analysis of BRUNOL3, a candidate gene for heart and thymus developmental defects associated with partial monosomy 10p [2].

Associations of CUGBP2 with chemical compounds

• These effects were reversed by NS398, a COX-2-specific inhibitor, suggesting that lipopolysaccharide-mediated inhibition of CUGBP2 is a PG-dependent mechanism [12].
• Dynamic antagonism between RNA-binding protein CUGBP2 and cyclooxygenase-2-mediated prostaglandin E2 in radiation damage [12].
• CUGBP2 binds apoB RNA, specifically an AU-rich sequence located immediately upstream of the edited cytidine [8].
• Five ethylene receptor genes, OS-ERS1, OS-ERS2, OS-ETR2, OS-ETR3, and OS-ETR4 were isolated and characterized from rice [13].
• The compound also effectively inhibited the biological and biochemical responses caused by another axonopathy inducer, colchicine, including tyrosine phosphorylation of Pyk2, formation of an 85-kDa poly(ADP-ribose)polymerase (PARP) fragment and apoptosis-associated induction of the NAPOR gene as well as neuronal cell death [14].

Other interactions of CUGBP2

• Genomic organization and isoform-specific tissue expression of human NAPOR (CUGBP2) as a candidate gene for familial arrhythmogenic right ventricular dysplasia [4].
• We identified a 20-residue region of CELF4 required for repression or activation, in contrast to ETR-3, for which the required residues are more disperse [15].
• We created minigenes for two of these genes, the CFTR and MTMR1 genes, and confirmed that ETR-3 regulates their splicing patterns [10].
• By using cellular models with a control- or DM1-like splicing pattern of Tau transcripts, we demonstrate that ETR-3 promotes selectively the exclusion of Tau exon 2 [3].
• The founder members of the family are the CUG-BP1 (CELF1) and ETR-3 (CELF2) proteins [16].

Analytical, diagnostic and therapeutic context of CUGBP2

• In situ hybridization of human embryos and fetuses revealed as well as in other tissues a strong expression of BRUNOL3 in thymus during different developmental stages [2].
• The differential expression of Brunol3 has been confirmed with real-time RT-PCR in spinal cord and muscle of three different models of spinal muscular atrophy [17].
• Among the five ethylene receptor genes, the expression levels of both OS-ETR3 and OS-ETR4 were too low to be detected by the northern blot analysis [13].
• Deduced amino acid sequences of OS-ERS1, OS-ERS2, OS-ETR2, OS-ETR3, and OS-ETR4 showed that they exhibited significant homology to the prokaryotic two-component signal transducer and a wide range of ethylene receptors in a variety of plant species [13].

References