Disease relevance of SR-A1

• Cloning of a gene (SR-A1), encoding for a new member of the human Ser/Arg-rich family of pre-mRNA splicing factors: overexpression in aggressive ovarian cancer [1].
• The CTD of human SR-A1 protein (aa 1187-1312), containing a conserved CTD-interaction domain and bearing a decahistidine (His10) tag was produced by DNA recombinant overexpression techniques in Escherichia coli from the vector pET16b and it was localized in the periplasmic space [2].
• To the best of our knowledge, this is the first study examining the expression of the novel gene SR-A1 in colon cancer progression [3].
• High SR-A1 expression was observed in 31/81 (38.3%) breast cancer tissues and was found to be more frequent in patients with tumors of large size (p=0.027), as well as in lymph node-positive patients (p=0.035) [4].
• Chinese hamster ovary cells stably transfected with human SR-A bound Escherichia coli and Staphylococcus aureus but ingested few organisms [5].

High impact information on SR-A1

• Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA) [6].
• Because all nucleotide changes in the mutants that disrupted SRA function were silent mutations presumed not to alter deduced encoded amino acid sequence, our analysis provides strong evidence that SRA-mediated coactivation is executed by distinct RNA motifs and not by an encoded protein [6].
• These findings support a role for mildly oxidized LDL in the redox regulation of macrophage differentiation and SR-A expression and suggest that increased vascular oxidative stress may contribute to the formation of both SMC and macrophage foam cells [7].
• Here we show that coincubation of SMC with macrophages or oxidized low density lipoproteins (LDL) from macrophage-conditioned medium activates these same regulatory pathways and stimulates SR-A expression [7].
• Oxidative stress caused by phorbol esters or reactive oxygen up-regulates the class A scavenger receptor (SR-A) in human smooth muscle cells (SMC), which normally do not express this receptor [7].

Chemical compound and disease context of SR-A1

• SR-A knockout (SR-A(-/-)) mice are more susceptible to endotoxic shock and Listeria monocytogenes infection in vivo, possibly due to decreased clearance of lipopolysaccharide and microorganisms, respectively [5].

Biological context of SR-A1

• In this study we examined the prognostic value of SR-A1 gene expression using a semi-quantitative RT-PCR method [4].
• Conversely, calcium ionophore greatly enhanced SR-A up-regulation by oxidized LDL or other treatments that promote intracellular oxidative stress [7].
• We have used flow cytometry to analyze the role of SR-A and other scavenger-like receptors in phagocytosis of bacteria in vitro [5].
• Phagocytosis and endocytosis via SR-A were markedly down-modulated when Mphi were plated on serum-coated tissue culture plastic compared to bacteriologic plastic, where cell adhesion is mediated by SR-A and CR3, respectively [5].
• Here, we present clinical, cytogenetic, and molecular data from a new CMPD1/SRA1 patient with t(6;17)(q14;q24) [8].

Anatomical context of SR-A1

• Furthermore, the mRNA of the SR-A1 gene in these cell lines appears to increase by estrogens, androgens and glucocorticoids, and to a lesser extend by progestins [1].
• Therefore, in the present study we examined the expression of the SR-A1 gene in colon cancer tissues by RT-PCR and found that it is overexpressed as compared to normal mucosa (p=0.01) [3].
• Using these antisera we show that the expression of SR-A protein is induced during monocyte to macrophage differentiation and that SR-A mediates 80% of the uptake of acetylated low density lipoprotein by human monocyte-derived macrophages [9].
• A specific and selective role for SR-A was shown, since bone marrow culture-derived Mphi from SR-A(-/-) mice ingested fewer E. coli organisms than did wild-type cells, while uptake of antibody-opsonized E. coli was unaffected [5].
• In contrast, among a scavenger receptor family, IL-4 as well as histamine up-regulated U937 cells to express the LOX-1 gene but not the SR-A gene, which genes encode receptors that scavenge oxidized lipids [10].

Associations of SR-A1 with chemical compounds

• Studies with the steroid hormone receptor-positive breast and prostate carcinoma cell lines ZR-75-1, BT-474 and LNCaP, respectively, suggest that SR-A1 is constitutively expressed [1].

Physical interactions of SR-A1

• Performing a pull-down assay we proved that the novel SR-A1 [1187-1312 His10] protein interacts with the CTD domain of RNA polymerase II [2].

Other interactions of SR-A1

• The SR-A1 protein contains an SR-rich domain as well as a CTD-binding domain present only in a subset of SR-proteins [1].
• Expression of the C-terminal domain of novel human SR-A1 protein: interaction with the CTD domain of RNA polymerase II [2].

Analytical, diagnostic and therapeutic context of SR-A1

• Follow-up analysis revealed that low SR-A1 expression increases the probability of both overall and disease-free survival of patients [4].
• The antisera recognize both type I and II SR-A in a wide range of immunological techniques [9].
• The fragment sequence of tie-1 promoter and human SR-A cDNA in plasmids pTie-1/hSR-A was correct and no ATG before the translation initiation sites of human SR-A was found by sequence analysis [11].

References