Disease relevance of CD3EAP

• Polymorphisms in the genes ERCC2, XRCC3 and CD3EAP influence treatment outcome in multiple myeloma patients undergoing autologous bone marrow transplantation [1].
• There were no common clinical features found in seven ASE-1 positive patients; however, 3 (43%) had a malignancy and 3 (43%) had slowly progressive systemic sclerosis [2].
• However, anti-dsDNA is associated with renal involvement, whereas ASE-1 reactivity shows an association with a history of serositis [3].
• Homozygous carriers of a haplotype consisting of ERCC1 Asn118Asn(A), ASE-1 G-21A(G), RAI IVS1 A4364G(A) are at increased risk of lung cancer especially among women [4].
• We show that autoantibodies to this antigen occur at a higher frequency in the sera of patients with SLE than in other systemic rheumatic diseases and that the specificity of ASE-1 as a serum marker of SLE increases as the number of epitopes recognized by the sera increases [3].

High impact information on CD3EAP

• CAST/hPAF49 can interact with activator upstream binding factor (UBF) and, weakly, with selectivity factor 1 (SL1) at the rDNA (ribosomal DNA repeat sequence encoding the 18S, 5.8S, and 28S rRNA genes) promoter [5].
• We provide evidence for growth-regulated Tyr phosphorylation of CAST/hPAF49, specifically in initiation-competent Pol Ibeta complexes in HeLa cells, at a conserved residue also known to be important for signaling during T-cell activation [5].
• Specific transcription from the mouse rRNA promoter in vitro was severely impaired by anti-PAF49 antibody, which was overcome by addition of recombinant PAF49 protein [6].
• The CLIP-170-like protein tip1p and the microtubule-bundling protein ase1p are required for this asymmetric regulation of microtubule dynamics, indicating contributions of factors both at microtubule plus ends and within the microtubule bundle [7].
• Ase1 localizes to microtubule overlapping zones and displays dynamic alterations of localization during the cell cycle [8].

Biological context of CD3EAP

• ASE-1: a novel protein of the fibrillar centres of the nucleolus and nucleolus organizer region of mitotic chromosomes [9].
• An open reading frame, without a translational start site, had been observed by others in this region of the chromosome 19 (19q13.3) and the putative protein was termed ASE-1 (Anti-Sense to ERCC-1) [9].
• Ase1, therefore, couples anaphase completion with cytokinesis upon cell division [8].
• In particular, its spindle localization during metaphase is reduced substantially, followed by robust appearance at the spindle midzone in anaphase. ase1 deletions are viable but defective in nuclear and septum positioning and completion of cytokinesis, which leads to diploidization and chromosome loss [8].
• This A/C polymorphism, which may affect mRNA stability for ERCC1, also results in an amino acid substitution of lysine to glutamine in a recently described nucleolar protein (ASE-1) and T-cell receptor complex subunit CD3epsilon-associated signal transducer (CAST) [10].

Anatomical context of CD3EAP

• This indicates that suboptimal repair of both DNA mechanisms favors prolonged TTF and that polymorphism in ERCC2, XRCC3 and CD3EAP predicts the outcome for patients treated with autologous stem cell transplantation [1].
• In contrast microtubule nucleating activities are not noticeably compromised in ase1 mutants [8].
• We have investigated the ability of an antisense oligonucleotide (ASE-1) to specifically inhibit IgE synthesis by a human myeloma cell line, U266 [11].

Associations of CD3EAP with chemical compounds

• ASE-1 was found to contain two domains that are present in a number of nucleolar specific proteins originating from a variety of organisms: a glycine-, arginine- and phenylalanine-rich putative nucleotide interaction domain and an alternating basic/acidic region [9].
• The Aurora kinase does not correctly localize to central spindles in the absence of Ase1 [8].
• METHODS: Cast specimens of aluminium bronzes with 1.4wt% Fe (G) and 4wt% Fe (N) were subject to progressively longer periods (up to in total 7 days) immersed in 0.1M saline, 0.1M lactic acid solutions and examined by scanning electron microscopy with EDX analysis [12].

Other interactions of CD3EAP

• In total, ASE-1 autoantibodies were found in 6/16 (37.5%) of confirmed NOR-90 sera from both cohorts [2].
• ASE-1 is a 55 kDa nucleolar autoantigen [3].

Analytical, diagnostic and therapeutic context of CD3EAP

• Indirect immunofluorescence analysis using antibodies generated to cloned regions of ASE-1 indicated that this protein occurs at the fibrillar centres of the nucleolus in interphase, the putative sites of rDNA transcription, and during cell division it is localized to the nucleolus organizer regions of the chromosomes [9].
• OBJECTIVE: The nucleolar proteins ASE-1 and NOR-90 can become confused because they have similar cytological and Western blot features [2].
• ASE-1 inhibited IgE production in a concentration-dependent manner, as assessed by isotype-specific ELISA measurement of immunoglobulin in myeloma cell supernatants [11].
• Effects of polymorphisms in ERCC1, ASE-1 and RAI on the risk of colorectal carcinomas and adenomas: a case control study [13].

References