ORCID Profile
0000-0001-8794-7173
Current Organisation
The University of Edinburgh
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Publisher: Springer Science and Business Media LLC
Date: 04-2000
DOI: 10.1038/74301
Abstract: Analysis of classical mouse mutations has been useful in the identification and study of many genes. We previously mapped Sox18, encoding an SRY-related transcription factor, to distal mouse chromosome 2. This region contains a known mouse mutation, ragged (Ra), that affects the coat and vasculature. Here we have directly evaluated Sox18 as a candidate for Ra. We found that Sox18 is expressed in the developing vascular endothelium and hair follicles in mouse embryos. Furthermore, we found no recombination between Sox18 and Ra in an interspecific backcross segregating for the Ra phenotype. We found point mutations in Sox18 in two different Ra alleles that result in missense translation and premature truncation of the encoded protein. Fusion proteins containing these mutations lack the ability to activate transcription relative to wild-type controls in an in vitro assay. Our observations implicate mutations in Sox18 as the underlying cause of the Ra phenotype, and identify Sox18 as a critical gene for cardiovascular and hair follicle formation.
Publisher: Proceedings of the National Academy of Sciences
Date: 24-05-2012
Abstract: Cellular proteins have been implicated as important for HIV-1 reverse transcription, but whether any are reverse transcription complex (RTC) cofactors or affect reverse transcription indirectly is unclear. Here we used protein fractionation combined with an endogenous reverse transcription assay to identify cellular proteins that stimulated late steps of reverse transcription in vitro. We identified 25 cellular proteins in an active protein fraction, and here we show that the eEF1A and eEF1G subunits of eukaryotic elongation factor 1 (eEF1) are important components of the HIV-1 RTC. eEF1A and eEF1G were identified in fractionated human T-cell lysates as reverse transcription cofactors, as their removal ablated the ability of active protein fractions to stimulate late reverse transcription in vitro. We observed that the p51 subunit of reverse transcriptase and integrase, two subunits of the RTC, coimmunoprecipitated with eEF1A and eEF1G. Moreover eEF1A and eEF1G associated with purified RTCs and colocalized with reverse transcriptase following infection of cells. Reverse transcription in cells was sharply down-regulated when eEF1A or eEF1G levels were reduced by siRNA treatment as a result of reduced levels of RTCs in treated cells. The combined evidence indicates that these eEF1 subunits are critical RTC stability cofactors required for efficient completion of reverse transcription. The identification of eEF1 subunits as unique RTC components provides a basis for further investigations of reverse transcription and trafficking of the RTC to the nucleus.
Publisher: Elsevier BV
Date: 2004
DOI: 10.1016/J.TIBS.2003.11.006
Abstract: It has been known for many years that aberrant levels of the factors involved in translation of mRNA can contribute to disease, most notably cancer. However, despite the wealth of information gathered about initiation and elongation factors from biochemical studies in mammalian cells, and from mutation analysis in lower organisms, little was known until recently about the effects that mutations in these factors could have on cellular function in higher organisms. In the past few years, this balance has started to be redressed, and we are at a fascinating stage in the molecular pathology of translation factors. It has been discovered recently that mutations in subunits of eukaryotic initiation factor 2B (eIF2B) underlie the neurodegenerative disease termed 'vanishing white matter'.
Publisher: Public Library of Science (PLoS)
Date: 12-2015
Publisher: Springer Science and Business Media LLC
Date: 1992
DOI: 10.1007/BF00648422
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.VIROL.2019.01.023
Abstract: The eukaryotic translation elongation factor 1A (eEF1A) has two cell-type specific paralogs, eEF1A1 and eEF1A2. Both paralogs undertake a canonical function in delivering aminoacyl-tRNA to the ribosome for translation, but differences in other functions are emerging. eEF1A1 has been reported to be important for the replication of many viruses, but no study has specifically linked the eEF1A2 paralog. We have previously demonstrated that eEF1A1 directly interacts with HIV-1 RT and supports efficient reverse transcription. Here, we showed that RT interacted more strongly with eEF1A1 than with eEF1A2 in immunoprecipitation assay. Biolayer interferometry using eEF1A paralogs showed different association and dissociation rates with RT. Over expressed eEF1A1, but not eEF1A2, was able to restore HIV-1 reverse transcription efficiency in HEK293T cells with endogenous eEF1A knocked-down and HIV-1 reverse transcription efficiency correlated with the level of eEF1A1 mRNA, but not to eEF1A2 mRNA in both HEK293T and primary human skeletal muscle cells.
Publisher: Springer Science and Business Media LLC
Date: 17-04-2007
Publisher: eLife Sciences Publications, Ltd
Date: 11-03-2022
Publisher: Springer Science and Business Media LLC
Date: 12-09-2005
Abstract: The tissue-specific translation elongation factor eEF1A2 was recently shown to be a potential oncogene that is overexpressed in ovarian cancer. Although there is no direct evidence for an involvement of eEF1A2 in breast cancer, the genomic region to which EEF1A2 maps, 20q13, is frequently lified in breast tumours. We therefore sought to establish whether eEF1A2 expression might be upregulated in breast cancer. eEF1A2 is highly similar (98%) to the near-ubiquitously expressed eEF1A1 (formerly known as EF1-α) making analysis with commercial antibodies difficult. We have developed specific anti-eEF1A2 antibodies and used them in immunohistochemical analyses of tumour s les. We report the novel finding that although eEF1A2 is barely detectable in normal breast it is moderately to strongly expressed in two-thirds of breast tumours. This overexpression is strongly associated with estrogen receptor positivity. eEF1A2 should be considered as a putative oncogene in breast cancer that may be a useful diagnostic marker and therapeutic target for a high proportion of breast tumours. The oncogenicity of eEF1A2 may be related to its role in protein synthesis or to its potential non-canonical functions in cytoskeletal remodelling or apoptosis.
Publisher: Springer Science and Business Media LLC
Date: 1993
DOI: 10.1007/BF00360830
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Catherine Abbott.