Anti-SRSF1 monoclonal antibody Made to order

Background: Preventive and therapeutic options for renal failure are still limited. Gene expression profile analysis is powerful in the identification of biological differences between end stage renal failure patients and healthy controls. Previous studies mainly used variance/regression analysis without considering various biological, environmental factors. The purpose of this study is to investigate the gene expression difference between end stage renal failure patients and healthy controls with partial least squares (PLS) based analysis. Methods: With gene expression data from the Gene Expression Omnibus database, we performed PLS analysis to identify differentially expressed genes. Enrichment and network analyses were also carried out to capture the molecular signatures of renal failure. Results: We acquired 573 differentially expressed genes. Pathway and Gene Ontology items enrichment analysis revealed over-representation of dysregulated genes in various biological processes. Network analysis identified seven hub genes with degrees higher than 10, including CAND1, CDK2, TP53, SMURF1, YWHAE, SRSF1, and RELA. Proteins encoded by CDK2, TP53, and RELA have been associated with the progression of renal failure in previous studies. Conclusions: Our findings shed light on expression character of renal failure patients with the hope to offer potential targets for future therapeutic studies.

Phosphorylation-dependent cell communication requires enzymes that specifically recognize key proteins in a sea of similar, competing substrates. The protein kinases achieve this goal by utilizing docking grooves in the kinase domain or heterologous protein adaptors to reduce 'off pathway' targeting. We now provide evidence that the nuclear protein kinase CLK1 (cell division cycle2-like kinase 1) important for splicing regulation departs from these classic paradigms by using a novel self-association mechanism. The disordered N-terminus of CLK1 induces oligomerization, a necessary event for targeting its physiological substrates the SR protein (splicing factor containing a C-terminal RS domain) family of splicing factors. Increasing the CLK1 concentration enhances phosphorylation of the splicing regulator SRSF1 (SR protein splicing factor 1) compared with the general substrate myelin basic protein (MBP). In contrast, removal of the N-terminus or dilution of CLK1 induces monomer formation and reverses this specificity. CLK1 self-association also occurs in the nucleus, is induced by the N-terminus and is important for localization of the kinase in sub-nuclear compartments known as speckles. These findings present a new picture of substrate recognition for a protein kinase in which an intrinsically disordered domain is used to capture physiological targets with similar disordered domains in a large oligomeric complex while discriminating against non-physiological targets.