The protein kinase DYRK1A phosphorylates the splicing factor SF3b1/SAP155 at Thr434, a novel in vivo phosphorylation site.

BACKGROUND: The U2 small nuclear ribonucleoprotein particle (snRNP) component SF3b1/SAP155 is the only spliceosomal protein known to be phosphorylated concomitant with splicing catalysis. DYRK1A is a nuclear protein kinase that has been localized to the splicing factor compartment. Here we describe the identification of DYRK1A as a protein kinase that phosphorylates SF3b1 in vitro and in cultivated cells. RESULTS: Overexpression of DYRK1A caused a markedly increased phosphorylation of SF3b1 in COS-7 cells as assessed by Western blotting with an antibody specific for phosphorylated Thr-Pro dipeptide motifs. Phosphopeptide mapping of metabolically labelled SF3b1 showed that the majority of the in vivo-phosphopeptides corresponded to sites also phosphorylated by DYRK1A in vitro. Phosphorylation with cyclin E/CDK2, a kinase previously reported to phosphorylate SF3b1, generated a completely different pattern of phosphopeptides. By mass spectrometry and mutational analysis of SF3b1, Thr434 was identified as the major phosphorylation site for DYRK1A. Overexpression of DYRK1A or the related kinase, DYRK1B, resulted in an enhanced phosphorylation of Thr434 in endogenous SF3b1 in COS-7 cells. Downregulation of DYRK1A in HEK293 cells or in HepG2 cells by RNA interference reduced the phosphorylation of Thr434 in SF3b1. CONCLUSION: The present data show that the splicing factor SF3b1 is a substrate of the protein kinase DYRK1A and suggest that DYRK1A may be involved in the regulation of pre mRNA-splicing.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Практический опыт развития комплексной системы экологического просвещения в образовательной организации

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Selenium Disulfide from Sustainable Resources: An Example of “Redneck” Chemistry with a Pinch of Salt

Selenium disulfide (often referred to as SeS2) encompasses a family of mixed selenium-sulfide eight-membered rings, traditionally used as an anti-dandruff agent in shampoos. SeS2 can be produced by reacting hydrogen sulfide (H2S) with selenite (SeO32−) under acidic conditions. This chemistry is also possible with natural spring waters that are rich in H2S, thus providing an avenue for the more sustainable, green production of high-quality SeS2 particles from an abundant natural source. The orange material obtained this way consists of small globules with a diameter in the range of 1.1 to 1.2 µm composed of various SexS8−x chalcogen rings. It shows the usual composition and characteristics of a Se-S interchalcogen compound in EDX and Raman spectroscopy. Since the mineral water from Bad Nenndorf is also rich in salts, the leftover brine has been evaporated to yield a selenium-enriched salt mixture similar to table salt. As the water from Bad Nenndorf—in comparison to other bodies of water around the world—is still rather modest in terms of its H2S content, especially when compared with volcanic waters, this approach may be refined further to become economically and ecologically viable, especially as a regional business model for small and medium-sized enterprises

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The regulation of SIRT2 function by cyclin-dependent kinases affects cell motility

Cyclin-dependent kinases (Cdks) fulfill key functions in many cellular processes, including cell cycle progression and cytoskeletal dynamics. A limited number of Cdk substrates have been identified with few demonstrated to be regulated by Cdk-dependent phosphorylation. We identify on protein expression arrays novel cyclin E–Cdk2 substrates, including SIRT2, a member of the Sirtuin family of NAD+-dependent deacetylases that targets α-tubulin. We define Ser-331 as the site phosphorylated by cyclin E–Cdk2, cyclin A–Cdk2, and p35–Cdk5 both in vitro and in cells. Importantly, phosphorylation at Ser-331 inhibits the catalytic activity of SIRT2. Gain- and loss-of-function studies demonstrate that SIRT2 interfered with cell adhesion and cell migration. In postmitotic hippocampal neurons, neurite outgrowth and growth cone collapse are inhibited by SIRT2. The effects provoked by SIRT2, but not those of a nonphosphorylatable mutant, are antagonized by Cdk-dependent phosphorylation. Collectively, our findings identify a posttranslational mechanism that controls SIRT2 function, and they provide evidence for a novel regulatory circuitry involving Cdks, SIRT2, and microtubules

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