Disease relevance of RERE

• In particular, further studies of the RERE gene and its products in HCV associated liver disease are warranted [1].
• Here we show that neuroblastoma tumor cell lines display reduced abundance of RERE transcripts [2].
• Our initial studies using a microtiter assay show that CAV exhibits a 50% inhibitory concentration of approximately 2 mM against the human pancreatic adenocarcinoma cell line, MIA PaCa-2, when these cells are grown in Dulbecco's modified Eagle's medium containing 0.4 mM ARG [3].
• The median peak GH response to ARG was significantly lower in the patients with idiopathic inflammatory pituitary stalk thickness (1.3 microg/liter; range, 0.8-1.8) than in those with craniopharyngioma (1.5 microg/liter; range, 1.1-1.6) or with LCH (2.8 microg/liter; range, 1.9-3.2, P = 0.00007) [4].
• This study aimed at evaluating the effects of ARG on the NO system and renal function in proteinuric patients with moderate chronic renal failure (CRF) [5].

Psychiatry related information on RERE

• In contrast to the PD + GHRH test, the ARG + GHRH test is reliable throughout the adult lifespan and appears to be the most appropriate for patient compliance and safety [6].

High impact information on RERE

• More RERE protein is recruited into nuclear aggregates of the DRPLA protein with extended polyglutamine than into those of pure polyglutamine [7].
• The gene isolated, designated RERE, has an open reading frame of 1566 amino acids, of which the C-terminal portion has 67% homology to DRPLA, whereas the N-terminal portion is distinctive [7].
• The ETV6/ARG protein may be involved in the unique differentiation capacity of this cell line [8].
• L-Canavanine (CAV), the L-2-amino-4-guanidinooxy structural analogue of L-arginine (ARG), is a potent ARG antagonist which occurs in the jack bean, Canavalia ensiformis [3].
• The pronounced increase in the ability of CAV to inhibit MIA PaCa-2 cell growth at the lower ARG concentration may result from enhanced CAV competition with ARG for incorporation into newly synthesized cellular proteins [3].

Chemical compound and disease context of RERE

• We evaluated the GH-releasing effect of GHRH plus arginine (ARG) in 36 patients (22 males and 14 females) with acquired GH deficiency including idiopathic inflammatory pituitary stalk thickness (n = 15), Langerhans cell histiocytosis (LCH) affecting the hypothalamic-pituitary area (n = 11), and craniopharyngioma (n = 10) [4].
• In spite of a reduction in body weight and IGF-I, insulin and glucose levels, in OB fasting failed to modify both the basal GH levels and the somatotroph responsiveness to GHRH when administered either alone or combined with ARG [9].
• Human APOBEC3G (hA3G) is a member of the APOBEC-1 related protein (ARP) family of cytidine deaminases. hA3G functions as a natural defense against endogenous retrotransposons and a multitude of retroviruses, most notably human immunodeficiency virus type 1 (HIV-1) [10].
• Juven, an enteral supplement which is a combination of beta-hydroxy-beta-methylbutyrate (HMB), arginine (ARG), and glutamine (GLN) has been shown to restore muscle in cachetic acquired immunodeficiency syndrome (AIDS) and cancer patients [11].
• Plasma ornithine (ORN), the AA more specifically linked to ARG metabolism, correlated with AAIR better than ARG and, for any given AAIR, was lower after trauma than after the development of sepsis [12].

Biological context of RERE

• Human RERE is localized to nuclear promyelocytic leukemia oncogenic domains and enhances apoptosis [2].
• We have independently identified RERE in a search for genes localized to the translocation breakpoint region at chromosome 1p36.2 in the neuroblastoma cell line NGP [2].
• These results identify RERE as a novel component of PODs and suggest an important role of RERE in the control of cell survival [2].
• Protein binding of a DRPLA family through arginine-glutamic acid dipeptide repeats is enhanced by extended polyglutamine [7].
• The DNB1/ARPh gene, which was found to be ubiquitously expressed in human adult and fetal tissues, is highly related to the DRPLA gene, in which expansion of a CAG triplet appears to be causal in the dentatorubral and pallidolysian atrophy disease phenotype [13].

Anatomical context of RERE

• FcR number and avidity were determined from Scatchard analysis of binding of 125I-labeled aggregated rat IgG (ARG) to macrophages [14].
• Physiologically relevant ARP26)levels promoted AChE gene expression and induced the expansion of cultured CD34+ progenitors and granulocyte maturation more effectively than cortisol, suggesting autoregulatory prolongation of ARP effects [15].
• MATERIALS AND METHODS: We studied the effects of stress, cortisol, antisense oligonucleotides to AChE, and synthetic ARP on peripheral blood cell composition and clonogenic progenitor status in mice under normal and stress conditions, and on purified CD34 cells of human origin [16].
• Ex vivo, ARP was more effective than cortisol and equally as effective as stem cell factor in promoting expansion and differentiation of early hematopoietic progenitor cells into myeloid and megakaryocyte lineages [16].
• In conclusion, plasma ARG concentrations and systemic NO synthesis were not deficient in preterm infants with BPD and signs of elevated pulmonary artery pressure [17].

Associations of RERE with chemical compounds

• RERE also contains arginine-aspartic acid (RD) dipeptide repeats and putative nuclear localization signal sequences, but no polyglutamine tracts [7].
• A major product of this process is a large nonaggregating species that consists of an NH2-terminal sequence beginning with ARG (and composed of about 100 residues of the interglobular domain) that is attached to an intact G2 domain followed by an extended section of the chondroitin sulfate-bearing domain toward the COOH terminus [18].
• Therefore, only GHRH combined with PD or ARG may be able to clearly differentiate normal children from patients with GH deficiency, though a normal GH response to these tests cannot rule out the existence of GH hyposecretory state because of hypothalamic dysfunction [19].
• During the six months of treatment, although a remarkable steadiness of ARG and NO3 levels was detected in the CRF-C group, the CRF-A group was characterized by a marked and immediate increase of plasma ARG [5].
• PAP increased FBF more than fourfold, but did not affect serum nitrite concentration (n = 11), whereas ARG significantly increased both FBF and nitrite [20].

Co-localisations of RERE

• Moreover, when RERE is overexpressed, the distribution of endogenous DRPLA protein alters from the diffused to the speckled pattern in the nucleus so as to co-localize with RERE [7].

Other interactions of RERE

• Hybridization screening resulted in the rapid and comprehensive identification of partial cDNAs of which a portion comprised two novel candidate genes, termed DNB1/ARPh and DNB5, which encode putative proteins of 1011 and 447 amino acids, respectively [13].
• Overexpression of RERE recruits a fraction of the proapoptotic protein BAX to PODS: This observation correlates with RERE-induced apoptosis, which occurs in a caspase-dependent manner [2].
• In contrast, ATN-2 displayed a bathochromic shift only with hemopexin [21].

Analytical, diagnostic and therapeutic context of RERE

• Immunoprecipitation and in vitro binding assays demonstrate that the DRPLA and RERE proteins bind each other, for which one of the RE repeats has a primary role, and extended polyglutamine enhances the binding [7].
• The aim of this study is to assess whether gender and body mass index (BMI) should be considered in developing thresholds to define GH deficiency, using GH responses to GHRH + arginine (ARG) stimulation and insulin tolerance test (ITT) [22].
• We employed in situ hybridization and immunocytochemical staining to monitor gene expression, and 5-bromo-2-deoxyuridine (BrdU), primary liquid cultures, and clonogenic progenitor assays to correlate AChE-R and ARP with proliferation and differentiation of hematopoietic progenitors [16].
• We found that Aph, Agl, and Atr1, but not Atr2 or Atr3, were significantly smaller in the OSA group than in the control group [23].
• These results were compared with those obtained by studying the effects of OGTT, Li-He and ARG on the GH response to GHRH-29 (1.0 micro g/kg i.v. at 0 min) [24].

References