Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Located at the 30 kb genomic region between complement factor B and component C4 are four ubiquitously expressed genes RD, SKI2W, DOM3Z and RP1. Besides RP1, the protein products of the other three genes each has highly conserved homologues or related proteins in lower eukaryotes, contains leucine zipper motifs for protein interaction, and plays important roles related to RNA metabolism. RD is a subunit of the negative transcription elongation factor, critical for the regulation of gene expression. It has an RNA recognition motif and 24 copies of Arg-Asp (RD) repeats. Ski2w is a nucleolar and cytoplasmic protein that has a putative RNA helicase domain. Fusion proteins of human Ski2w expressed in insect cells and bacteria have ATPase activity. The cytoplasmic protein of human Ski2w is associated with the polysomes and probably the 40S subunit of ribosomes. Ski2w is probably involved in the regulation of translation and RNA turnover. Dom3z is a nuclear protein whose yeast homologue forms a complex with an exoribonuclease. RP1 (or STK19) is a Ser/Thr nuclear protein kinase. No homologues of RP1 in lower eukaryotes have been discovered. Six polymorphic residues are present in human Ski2w and two in Dom3z. The potential roles of Ski2w and Dom3z on the clearance of degraded nuclear and cytoplasmic RNA raised their possibilities as susceptibility genes of systemic lupus erythematosus that is a disease with flawed processes in the removal of apoptotic materials.
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PMID:Features of the two gene pairs RD-SKI2W and DOM3Z-RP1 located between complement component genes factor B and C4 at the MHC class III region. 1148 1

Elongation factor 2 kinase (eEF-2K), also known as calmodulin-dependent protein kinase III, is a member of the calmodulin-mediated signaling pathway that links activation of cell surface receptors to cell division. The activity of eEF-2K is increased in many human cancers and may be a valid target for anti-cancer treatment. It is one of the unconventional eukaryotic protein kinases with respect to its structural domains in comparison to other members of the serine/threonine protein kinase superfamily. eEF-2K is highly conserved in nature. For example, the amino acid sequence of human eEF-2K is 90% identical to mouse and rat eEF-2Ks and 40% identical to that of the C. elegans enzyme. Therefore it has been difficult to generate high-titer and high-specificity antibodies to the human enzyme by traditional techniques. Patients with systemic lupus erythematosus (SLE) produce auto-antibodies to a variety of cellular proteins, including members of the protein translation apparatus. Hence, we developed an ELISA assay that could detect anti-eEF2K antibodies from sera of SLE patients using purified eEF-2K as an antigen. We screened 117 sera from SLE patients. High-titer anti-eEF-2K antibodies were detected in 72 subjects. One of the high-titer sera was used for further characterization. The auto-antibody recognized eEF-2K on immunoblots and immunoprecipitated the kinase with intact enzyme activity. In conclusion, anti-eEF-2K antibodies are found in sera of SLE patients and are useful tools to study the role of this highly conserved enzyme.
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PMID:Detection of anti-elongation factor 2 kinase (calmodulin-dependent protein kinase III) antibodies in patients with systemic lupus erythematosus. 1205 69

We previously demonstrated that coxsackievirus B3 (CVB3) infection upregulated heat shock protein 70 (Hsp70) and promoted CVB3 multiplication. Here, we report the underlying mechanism by which Hsp70 enhances viral RNA translation. By using an Hsp70-overexpressing cell line infected with CVB3, we found that Hsp70 enhanced CVB3 VP1 translation at two stages. First, Hsp70 induced upregulation of VP1 translation at the initiation stage via upregulation of internal ribosome entry site trans-acting factor lupus autoantigen protein and activation of eIF4E binding protein 1, a cap-dependent translation suppressor. Second, we found that Hsp70 increased CVB3 VP1 translation by enhancing translation elongation. This was mediated by the Akt-mammalian target of rapamycin complex 1 signal cascade, which led to the activation of eukaryotic elongation factor 2 via p70S6K- and cell division cycle protein 2 homolog (Cdc2)-mediated phosphorylation and inactivation of eukaryotic elongation factor 2 kinase. We also determined the position of Cdc2 in this signal pathway, indicating that Cdc2 is regulated by mammalian target of rapamycin complex 1. This signal transduction pathway was validated using a number of specific pharmacological inhibitors, short interfering RNAs (siRNAs) and a dominant negative Akt plasmid. Because Hsp70 is a central component of the cellular network of molecular chaperones enhancing viral replication, these data may provide new strategies to limit this viral infection.
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PMID:Heat shock protein 70 promotes coxsackievirus B3 translation initiation and elongation via Akt-mTORC1 pathway depending on activation of p70S6K and Cdc2. 2809 7