This finding indicates that this inhibitor recognized the particular enzymesubstrate complex

This finding indicates that this inhibitor recognized the particular enzymesubstrate complex

ed mouse model systems such as inducible and/or tissue specific knockouts.183 There is also a need for transgenic mice model systems that overexpress splicing factors. One recent www.tandfonline.com Molecular & Cellular Oncology e970955-7 example is the inducible transgenic SRSF6 mouse model, in which overexpression of this oncogenic SR protein was shown to induce skin hyperplasia.42 In vitro modulation, such as overexpression or knockdown, is more common and has been used extensively, but has limitations. For example, the expression of some splicing factors is tightly regulated, with some factors autoregulating their own expression. New techniques, such as crosslinking immunoprecipitation and modifications of CLIP, have been established to identify mRNA targets of splicing factors and characterize their cis-acting sequences.184-192 Results of these studies will surely be applied to cancer research. The recent identification of INK-128 web recurrent mutations in spliceosomal components16-22 reinforces the recognition of splicing factors as important drivers of cancer development and progression and as promising targets for the development of anticancer drugs. In this regard, newly identified alternative splicing events that contribute to cancer initiation and/or progression present promising targets for splicing modulation using modified antisense RNA oligos as described above. Resources such as The Cancer Genome Atlas, which contains RNA-seq data from hundreds of tumors and corresponding normal tissues, will contribute to the identification of new alternative splicing events that drive tumor formation and maintenance. Modulation of these splicing events by antisense oligonucleotides or small molecules presents a new approach for cancer therapy. Moreover, over the past PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19840835 few years increasing lines of evidence have suggested that splicing Increased complexity of alternative splicing during evolution and the expansion of the SR-protein kinases When comparing single-cell eukaryotes like the yeast S. cerevisae,1 to metazoans of increasing complexity, there appears to be a general relationship between increased complexity of the organism and the number of genes. After the human genome was sequenced in 2001, it was found that our genome contains approximately 23,000 genes, a much lower Dale P Corkery, Alice C Holly, Sara Lahsaee, and Graham Dellaire Correspondence to: Graham Dellaire; Email: [email protected] Submitted: 05/01/2015; Revised: 06/03/2015; Accepted: 06/08/2015 http://dx.doi.org/10.1080/19491034.2015.1062194 This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author have been asserted. number than expected.2 The human genome is larger than the genome of the fly D. melanogaster and comparable to the genome of the worm C. elegans.3,4 At the same time, it was discovered that genes containing introns encode many possible transcripts, which arise by alternative mRNA splicing and allow organisms with a similar number of genes to have more complex and diverse proteomes as a result of mRNA splicing. The potential of alternative mRNA splicing to increase protein diversity is most clearly illustrated by the extreme example of the fly axonal guidance gene Down syndrome cell adhesion molecule 1, which is predicted to produce u

Proton-pump inhibitor

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