For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
49
views
108
references
 Top references
cited by
12
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      479
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Splicing Regulators and Their Roles in Cancer Biology and Therapy

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Alternative splicing allows cells to expand the encoding potential of their genomes. In this elegant mechanism, a single gene can yield protein isoforms with even antagonistic functions depending on the cellular physiological context. Alterations in splicing regulatory factors activity in cancer cells, however, can generate an abnormal protein expression pattern that promotes growth, survival, and other processes, which are relevant to tumor biology. In this review, we discuss dysregulated alternative splicing events and regulatory factors that impact pathways related to cancer. The SR proteins and their regulatory kinases SRPKs and CLKs have been frequently found altered in tumors and are examined in more detail. Finally, perspectives that support splicing machinery as target for the development of novel anticancer therapies are discussed.

          Related collections

          Most cited references108

          • Record: found
          • Abstract: found
          • Article: not found

          Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged.

          Charles J David, James Manley (2010)
          Alternative splicing of mRNA precursors is a nearly ubiquitous and extremely flexible point of gene control in humans. It provides cells with the opportunity to create protein isoforms of differing, even opposing, functions from a single gene. Cancer cells often take advantage of this flexibility to produce proteins that promote growth and survival. Many of the isoforms produced in this manner are developmentally regulated and are preferentially re-expressed in tumors. Emerging insights into this process indicate that pathways that are frequently deregulated in cancer often play important roles in promoting aberrant splicing, which in turn contributes to all aspects of tumor biology.
          Article 0 comments Cited 346 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Splicing in disease: disruption of the splicing code and the decoding machinery.

            Guey-Shin Wang, Thomas Cooper (2007)
            Human genes contain a dense array of diverse cis-acting elements that make up a code required for the expression of correctly spliced mRNAs. Alternative splicing generates a highly dynamic human proteome through networks of coordinated splicing events. Cis- and trans-acting mutations that disrupt the splicing code or the machinery required for splicing and its regulation have roles in various diseases, and recent studies have provided new insights into the mechanisms by which these effects occur. An unexpectedly large fraction of exonic mutations exhibit a primary pathogenic effect on splicing. Furthermore, normal genetic variation significantly contributes to disease severity and susceptibility by affecting splicing efficiency.
            Article 0 comments Cited 342 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes.

              Philippe Bouillet, Jared Purton, Dale Godfrey … (2002)
              During lymphocyte development, the assembly of genes coding for antigen receptors occurs by the combinatorial linking of gene segments. The stochastic nature of this process gives rise to lymphocytes that can recognize self-antigens, thereby having the potential to induce autoimmune disease. Such autoreactive lymphocytes can be silenced by developmental arrest or unresponsiveness (anergy), or can be deleted from the repertoire by cell death. In the thymus, developing T lymphocytes (thymocytes) bearing a T-cell receptor (TCR)-CD3 complex that engages self-antigens are induced to undergo programmed cell death (apoptosis), but the mechanisms ensuring this 'negative selection' are unclear. We now report that thymocytes lacking the pro-apoptotic Bcl-2 family member Bim (also known as Bcl2l11) are refractory to apoptosis induced by TCR-CD3 stimulation. Moreover, in transgenic mice expressing autoreactive TCRs that provoke widespread deletion, Bim deficiency severely impaired thymocyte killing. TCR ligation upregulated Bim expression and promoted interaction of Bim with Bcl-XL, inhibiting its survival function. These findings identify Bim as an essential initiator of apoptosis in thymocyte-negative selection.
              Article 0 comments Cited 169 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Biomed Res Int
                Journal ID (iso-abbrev): Biomed Res Int
                Journal ID (publisher-id): BMRI
                Title: BioMed Research International
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 2314-6133
                ISSN (Electronic): 2314-6141
                Publication date (Print): 2015
                Publication date (Electronic): 26 July 2015
                Volume: 2015
                Electronic Location Identifier: 150514
                Affiliations
                1Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, 36570-900 Viçosa, MG, Brazil
                2Departamento de Química, Universidade Federal de Viçosa, 36570-900 Viçosa, MG, Brazil
                3Departamento de Veterinária, Universidade Federal de Viçosa, 36570-900 Viçosa, MG, Brazil
                Author notes
                *Gustavo Costa Bressan: gustavo.bressan@ 123456ufv.br

                Academic Editor: Maria Paola Paronetto

                Article
                DOI: 10.1155/2015/150514
                PMC ID: 4529883
                PubMed ID: 26273588
                SO-VID: e5b673ac-4414-4313-bf81-208c3b477e82
                Copyright © Copyright © 2015 Maria Roméria da Silva et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 28 November 2014
                Date revision received : 10 March 2015
                Date accepted : 1 April 2015
                Categories
                Subject: Review Article

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content479

                See all similar

                Cited by19

                See all cited by

                Most referenced authors1,430

                See all reference authors