Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autocrine products of osteoclasts such as interleukin-6 may play an important role in normal osteoclast formation and activity. To identify novel stimulatory factors for osteoclasts, we have prepared a mammalian cDNA expression library generated from highly purified human osteoclast-like multinucleated cells (MNC) formed in long term bone marrow cultures and screened this library for autocrine factors that enhance MNC formation. A candidate clone which stimulated MNC formation was isolated. Sequence analysis showed that this cDNA encoded annexin II (AXII). Purified recombinant AXII significantly increased MNC formation in human bone marrow cultures in the absence of 1,25-(OH)2 vitamin D3 and enhanced MNC formation in mouse bone marrow cultures treated with 10(-9) M 1,25-(OH)2 vitamin D3. The enhanced MNC formation in murine marrow cultures resulted in increased bone resorption. Treatment of fetal rat long bones with AXII and 1,25-(OH)2 vitamin D3 significantly increased bone resorption compared to 1,25-(OH)2 vitamin D3 alone. Reverse transcriptase polymerase chain reaction analysis demonstrated that AXII mRNA was expressed at high levels in RNA isolated from highly purified giant cells from osteoclastomas, human osteoclast-like MNC, and pagetic bone. Western blot analysis of conditioned media collected from human marrow cultures showed that AXII was present in the media. Furthermore, approximately 50% of total AXII produced by cells transfected with AXII cDNA was present in the conditioned media. These data suggest that the AXII is an autocrine factor that enhances osteoclast formation and bone resorption and demonstrate a previous unknown function for AXII.
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PMID:Cloning and identification of annexin II as an autocrine/paracrine factor that increases osteoclast formation and bone resorption. 796 21

Annexin A2 (ANXA2) is a Ca(2+)-binding protein that is up-regulated in virally transformed cell lines and in human tumors. Here, we show that ANXA2 binds directly to both ribonucleotide homopolymers and human c-myc RNA. ANXA2 was shown to bind specifically to poly(G) with high affinity (K(d) = 60 nM) and not to poly(A), poly(C), or poly(U). The binding of ANXA2 to poly(G) required Ca(2+) (A(50%) = 10 microM). The presence of RNA in the immunoprecipitates of ANXA2 isolated from HeLa cells established that ANXA2 formed a ribonucleoprotein complex in vivo. Sucrose gradient analysis showed that ANXA2 associates with ribonucleoprotein complexes and not with polyribosomes. Reverse transcriptase-PCR identified c-myc mRNA as a component of the ribonucleoprotein complex formed by ANXA2 in vivo, and binding studies confirmed a direct interaction between ANXA2 and c-myc mRNA. Transfection of LNCaP cells with the ANXA2 gene resulted in the up-regulation of c-Myc protein. These findings identify ANXA2 as a Ca(2+)-dependent RNA-binding protein that interacts with the mRNA of the nuclear oncogene, c-myc.
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PMID:Annexin A2 is a novel RNA-binding protein. 1467 33

Non-structural protein 9 (Nsp9), a RNA-dependent RNA polymerase (RdRp) of the porcine reproductive and respiratory syndrome virus (PRRSV), is necessary for PRRSV replication. However, the binding partners of Nsp9 have not been identified. In this study, seven host proteins were identified as Nsp9-binding proteins using yeast two-hybrid (Y2H). Among of them, we confirmed the interaction of Nsp9 with Annexin A2 (ANXA2) using Y2H, Co-immunoprecipitation (Co-IP), GST pulldown and immunofluorescence assay (IFA). We found that only full-length ANXA2 could bind with Nsp9 in vitro and Nsp9 interacted with endogenous ANXA2 in PRRSV-infected MARC-145 cells. In addition, we found that the Nsp9-ANXA2 interaction was partially reduced by RNase A treatment. Furthermore, PRRSV growth was significantly hindered in ANXA2-knockdown MARC-145 cells. Taken together, these results indicate that Nsp9 binding partner ANXA2 is beneficial for PRRSV replication.
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PMID:The interaction between host Annexin A2 and viral Nsp9 is beneficial for replication of porcine reproductive and respiratory syndrome virus. 2487 99