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      DExD/H box RNA helicases: multifunctional proteins with important roles in transcriptional regulation

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      Nucleic Acids Research
      Oxford University Press

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          Abstract

          The DExD/H box family of proteins includes a large number of proteins that play important roles in RNA metabolism. Members of this family have been shown to act as RNA helicases or unwindases, using the energy from ATP hydrolysis to unwind RNA structures or dissociate RNA–protein complexes in cellular processes that require modulation of RNA structures. However, it is clear that several members of this family are multifunctional and, in addition to acting as RNA helicases in processes such as pre-mRNA processing, play important roles in transcriptional regulation. In this review I shall concentrate on RNA helicase A (Dhx9), DP103 (Ddx20), p68 (Ddx5) and p72 (Ddx17), proteins for which there is a strong body of evidence showing that they play important roles in transcription, often as coactivators or corepressors through their interaction with key components of the transcriptional machinery, such as CREB-binding protein, p300, RNA polymerase II and histone deacetylases.

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          A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.

          A strong candidate for the 17q-linked BRCA1 gene, which influences susceptibility to breast and ovarian cancer, has been identified by positional cloning methods. Probable predisposing mutations have been detected in five of eight kindreds presumed to segregate BRCA1 susceptibility alleles. The mutations include an 11-base pair deletion, a 1-base pair insertion, a stop codon, a missense substitution, and an inferred regulatory mutation. The BRCA1 gene is expressed in numerous tissues, including breast and ovary, and encodes a predicted protein of 1863 amino acids. This protein contains a zinc finger domain in its amino-terminal region, but is otherwise unrelated to previously described proteins. Identification of BRCA1 should facilitate early diagnosis of breast and ovarian cancer susceptibility in some individuals as well as a better understanding of breast cancer biology.
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            AP-1: a double-edged sword in tumorigenesis.

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              The ETS-domain transcription factor family.

              ETS-domain transcription-factor networks represent a model for how combinatorial gene expression is achieved. These transcription factors interact with a multitude of co-regulatory partners to elicit gene-specific responses and drive distinct biological processes. These proteins are controlled by a complex series of inter and intramolecular interactions, and signalling pathways impinge on these proteins to further regulate their action.
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Research
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                September 2006
                September 2006
                25 August 2006
                : 34
                : 15
                : 4206-4215
                Affiliations
                Cancer Biology Group, Division of Pathology and Neuroscience, University of Dundee, Ninewells Hospital and Medical School Dundee DD1 9SY, UK
                Author notes
                *Tel: +44 1382 496370; Fax: +44 1382 566933; Email: f.v.fullerpace@ 123456dundee.ac.uk
                Article
                10.1093/nar/gkl460
                1616952
                16935882
                a5b4cea8-dd8c-489e-b595-0a66a4c8ae01
                © 2006 The Author(s)

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 March 2006
                : 13 June 2006
                : 16 June 2006
                Categories
                Survey and Summary

                Genetics
                Genetics

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