Research Topics
Genomes and Genes
| Andrew D SharrocksSummaryAffiliation: University of Manchester Country: UK Publications
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Detail Information
Publications
ERK5 is targeted to myocyte enhancer factor 2A (MEF2A) through a MAPK docking motifDalia Barsyte-Lovejoy
School of Biological Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK
Biochem J 381:693-9. 2004..Our data therefore extend previous observations on other MAPKs and demonstrate that the requirement for specific docking domains in promoting MAPK action towards substrates is a general property of MAPKs...
Cell cycle: sustained ERK signalling represses the inhibitorsAndrew D Sharrocks
Faculty of Life Sciences, University of Manchester, UK
Curr Biol 16:R540-2. 2006..A recent study has shown that cell cycle re-entry requires the downregulation of an anti-proliferative gene cluster following sustained activation of the ERK pathway...
Docking domains and substrate-specificity determination for MAP kinasesA D Sharrocks
School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester, UK M13 9PT
Trends Biochem Sci 25:448-53. 2000..Additional specificity determinants in the substrates serve to enhance the specificity of substrate phosphorylation by MAP kinases further...
Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal LectureAndrew D Sharrocks
School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester M13 9PT, U K
Biochem Soc Trans 30:1-9. 2002....
The ETS-domain transcription factor familyA D Sharrocks
School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester, M13 9PT, UK
Nat Rev Mol Cell Biol 2:827-37. 2001..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...
Ternary complex factor-serum response factor complex-regulated gene activity is required for cellular proliferation and inhibition of apoptotic cell deathElaine R Vickers
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Rd, Manchester M13 9PT, United Kingdom
Mol Cell Biol 24:10340-51. 2004..Thus, our data confirm a role for TCF-SRF-regulated gene activity in regulating proliferation and provide further evidence to indicate a role in protecting cells from apoptotic cell death...
A competitive transcription factor binding mechanism determines the timing of late cell cycle-dependent gene expressionZoulfia Darieva
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M139PT, UK
Mol Cell 38:29-40. 2010....
Polo kinase controls cell-cycle-dependent transcription by targeting a coactivator proteinZoulfia Darieva
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK
Nature 444:494-8. 2006..Thus, polo kinase is required for the production of key mitotic regulators, in addition to previously defined roles in controlling other mitotic events...
Elucidation of the ELK1 target gene network reveals a role in the coordinate regulation of core components of the gene regulation machineryJoanna Boros
Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
Genome Res 19:1963-73. 2009....
SUMO promotes HDAC-mediated transcriptional repressionShen Hsi Yang
School of Biological Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom
Mol Cell 13:611-7. 2004..Thus, our data demonstrate an important integration point for two protein-modifying pathways in the cell, the SUMO and deacetylation pathways, that combine to promote transcriptional repression...
Protein kinase C regulates late cell cycle-dependent gene expressionZoulfia Darieva
University of Manchester, Manchester, United Kingdom
Mol Cell Biol 32:4651-61. 2012..This study therefore identifies an important role for Pkc1p in controlling the correct temporal expression of genes in the cell cycle...
Cell cycle-regulated transcription through the FHA domain of Fkh2p and the coactivator Ndd1pZoulfia Darieva
School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester M13 9PT, United Kingdom
Curr Biol 13:1740-5. 2003..Our data therefore link the transcriptional activity of the FHA domain with cell cycle-dependent phosphorylation of the coactivator Ndd1p and reveal a mechanism that permits precise temporal activation of the Mcm1p-Fkh2p complex...
The ETS domain transcription factor Elk-1 contains a novel class of repression domainShen Hsi Yang
School of Biological Sciences, University of Manchester, 2205 Stopford Building, Oxford Road, Manchester M13 9PT, UK
Mol Cell Biol 22:5036-46. 2002..Thus, the Elk-1 R motif and the p300 CRD1 motif represent a new class of repression domains that are regulated in a context-dependent manner...
PIASxalpha differentially regulates the amplitudes of transcriptional responses following activation of the ERK and p38 MAPK pathwaysShen Hsi Yang
Faculty of Life Sciences, University of Manchester, UK
Mol Cell 22:477-87. 2006..Thus, PIASxalpha acts as a key signal integrator that permits different responses from the same transcription factor, depending on the signaling pathway that is activated...
PIASx acts as an Elk-1 coactivator by facilitating derepressionShen Hsi Yang
Faculty of Life Sciences, University of Manchester, Manchester, UK
EMBO J 24:2161-71. 2005..Our data therefore reveal a novel coactivator function for PIASx(alpha) through reversing SUMO-mediated repression of transcription factor activity...
Regulation of TCF ETS-domain transcription factors by helix-loop-helix motifsJulie Stinson
School of Biological Sciences, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK
Nucleic Acids Res 31:4717-28. 2003....
Cell cycle-dependent regulation of the forkhead transcription factor FOXK2 by CDK·cyclin complexesAnett Marais
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom
J Biol Chem 285:35728-39. 2010..These two CDK sites appear vital for FOXK2 function because expression of a mutant lacking these sites cannot be tolerated and causes apoptosis...
MAP Kinase: SUMO pathway interactionsShen Hsi Yang
Faculty of Life Sciences, University of Manchester, Manchester, UK
Methods Mol Biol 661:343-67. 2010..Here, we describe protocols that can be used in studying the cross talk between the MAPK and SUMO pathways, particularly at the level of gene regulation...
The SUMO E3 ligase activity of Pc2 is coordinated through a SUMO interaction motifShen Hsi Yang
Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom
Mol Cell Biol 30:2193-205. 2010..The significance of the SIM2-dependent functions of Pc2 is demonstrated in the control of the precise expression of lineage-specific genes during embryonic stem cell differentiation...
Extracellular signal-regulated kinase mitogen-activated protein kinase signaling initiates a dynamic interplay between sumoylation and ubiquitination to regulate the activity of the transcriptional activator PEA3Baoqiang Guo
Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom
Mol Cell Biol 29:3204-18. 2009....
SENP1 participates in the dynamic regulation of Elk-1 SUMOylationJames Witty
Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U K
Biochem J 428:247-54. 2010..Taken together, these results therefore reveal an important role for SENP1 in the regulation of Elk-1-mediated gene expression in response to mitogenic signalling cues...
SUMO and transcriptional repression: dynamic interactions between the MAP kinase and SUMO pathwaysShen-Hsi Yang
School of Biological Sciences, University of Manchester, Manchester, M13 9PT UK
Cell Cycle 2:528-30. 2003..However, the mechanism by which SUMO promotes transcriptional repression remains enigmatic...
The forkhead transcription factor FOXM1 controls cell cycle-dependent gene expression through an atypical chromatin binding mechanismXi Chen
University of Manchester, Manchester, United Kingdom
Mol Cell Biol 33:227-36. 2013..Thus, we have uncovered a novel and unexpected mode of chromatin binding of a FOX transcription factor that allows it to specifically control cell cycle-dependent gene expression...
An extended consensus motif enhances the specificity of substrate modification by SUMOShen Hsi Yang
Faculty of Life Sciences, University of Manchester, Manchester, UK
EMBO J 25:5083-93. 2006..We demonstrate that this extended motif can be used to correctly predict novel targets for SUMO modification...
Dynamic interplay of the SUMO and ERK pathways in regulating Elk-1 transcriptional activityShen Hsi Yang
School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester M13 9PT, United Kingdom
Mol Cell 12:63-74. 2003..Thus, the reciprocal regulation of the activation and repressive activities are coupled by MAP kinase modification of Elk-1...
The forkhead transcription factor FOXK2 promotes AP-1-mediated transcriptional regulationZongling Ji
University of Manchester, Manchester, United Kingdom
Mol Cell Biol 32:385-98. 2012..In this context, FOXK2 is required for the efficient recruitment of AP-1 to chromatin. Thus, we have uncovered an important new molecular mechanism that controls AP-1-dependent gene expression...
Molecular determinants of the cell-cycle regulated Mcm1p-Fkh2p transcription factor complexJoanna Boros
School of Biological Sciences, University of Manchester, 2 205 Stopford Building, Oxford Road, Manchester M13 9PT, UK
Nucleic Acids Res 31:2279-88. 2003..Our data therefore provide molecular insights into the mechanisms of Mcm1p- Fkh2p complex formation and more generally aid our understanding of MADS-box protein function...
The use of inducible engrailed fusion proteins to study the cellular functions of eukaryotic transcription factorsElaine R Vickers
School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester, M13 9PT, UK
Methods 26:270-80. 2002..Here we illustrate this integrated approach by using a conditional dominant-negative Elk-1 protein to identify candidate Elk-1-regulated target genes...
MAP kinase-mediated c-fos regulation relies on a histone acetylation relay switchAmanda O'Donnell
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK
Mol Cell 29:780-5. 2008....
Overlapping promoter targeting by Elk-1 and other divergent ETS-domain transcription factor family membersJoanna Boros
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK
Nucleic Acids Res 37:7368-80. 2009....
Rev7/MAD2B links c-Jun N-terminal protein kinase pathway signaling to activation of the transcription factor Elk-1Lin Zhang
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom
Mol Cell Biol 27:2861-9. 2007....
ELK1 uses different DNA binding modes to regulate functionally distinct classes of target genesZaneta Odrowaz
Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom
PLoS Genet 8:e1002694. 2012..We have therefore uncovered an unexpected link between the type of binding mode employed by a transcription factor, the subsequent gene regulatory mechanisms used, and the functional categories of target genes controlled...
Specificity determinants in MAPK signaling to transcription factorsDalia Barsyte-Lovejoy
School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
J Biol Chem 277:9896-903. 2002..A model is proposed to explain how specificity is generated within these short docking domains...
Transcriptional regulation by the MAP kinase signaling cascadesShen-Hsi Yang
School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester M13 9PT, UK
Gene 320:3-21. 2003..In this review, we summarise the current knowledge of MAPK-mediated gene regulation, and focus on how complexities in signaling outcomes are achieved and how this relates to physiological processes...
The ETS domain transcription factor Elk-1 regulates the expression of its partner protein, SRFAneta Kasza
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom
J Biol Chem 280:1149-55. 2005..Our data therefore reveal that SRF is an important target for the ERK and Rho signaling pathways that converge on a ternary TCF-SRF complex at the SRE on the SRF promoter...
The LIM domain protein LPP is a coactivator for the ETS domain transcription factor PEA3Baoqiang Guo
Faculty of Life Sciences, University of Manchester, Michael Smith Bldg, Oxford Road, Manchester M13 9PT, United Kingdom
Mol Cell Biol 26:4529-38. 2006..As LPP continually shuttles between the cell periphery and the nucleus, it represents a potential novel link between cell surface events and changes in gene expression...
The ERK MAP kinase-PEA3/ETV4-MMP-1 axis is operative in oesophageal adenocarcinomaRichard Keld
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, UK
Mol Cancer 9:313. 2010..The PEA3 subfamily of ETS-domain transcription factors have been implicated in tumour metastasis in several different cancers...
MAP kinase signalling cascades and transcriptional regulationShen Hsi Yang
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK
Gene 513:1-13. 2013..Finally, we summarise progress in studying the physiological functions of key MAPK transcriptional targets...
Functional interactions between the Forkhead transcription factor FOXK1 and the MADS-box protein SRFCecilie T Freddie
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK
Nucleic Acids Res 35:5203-12. 2007..Thus FOXK1 represents an additional member of the growing repertoire of transcription factors that can interact with SRF and modulate the transcriptional output from SRF-regulated promoters...
Assembly of transcription factor IIB at a promoter in vivo requires contact with RNA polymerase IILaura M Elsby
Faculty of Life Sciences, The Michael Smith Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK
EMBO Rep 7:898-903. 2006..Together, our results support a mode of preinitiation complex assembly in which TFIIB/RNA polymerase II recruitment to the promoter occurs in vivo...
Immediate-early gene activation by the MAPK pathways: what do and don't we know?Amanda O'Donnell
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK
Biochem Soc Trans 40:58-66. 2012..We highlight important fundamental regulatory principles, but also illustrate the gaps in our current knowledge and the potential danger in making assumptions based on extrapolation from disparate studies...
Dynamic modification of the ETS transcription factor PEA3 by sumoylation and p300-mediated acetylationBaoqiang Guo
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK
Nucleic Acids Res 39:6403-13. 2011..However, despite the mutually exclusive nature of these modifications, both contribute to the trans-activation capacity of PEA3, implying that a dynamic series of modification events occurs during the activation process...
Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescenceN Ohtani
Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK
Nature 409:1067-70. 2001..11). In senescent cells, where the Ets2 levels and MEK signalling decline, the marked increase in p16INK4a expression is consistent with the reciprocal reduction of Id1 and accumulation of Ets1...
Understanding cancer: from the gene to the organism. Conference on genes and cancerIain Hagan
School of Biological Sciences, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK
EMBO Rep 3:415-9. 2002
Selective targeting of MAPKs to the ETS domain transcription factor SAP-1A Galanis
School of Biological Sciences, University of Manchester, Manchester M13 9PT and the School of Biochemistry and Genetics, Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom
J Biol Chem 276:965-73. 2001..Our data therefore demonstrate that a modular system of motifs is responsible for directing specific MAPK subtypes to SAP-1, but also point to important distinctions in the mechanism of action of the D-domain and FXF motif...
Temporal recruitment of the mSin3A-histone deacetylase corepressor complex to the ETS domain transcription factor Elk-1S H Yang
School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
Mol Cell Biol 21:2802-14. 2001..Elk-1 therefore undergoes temporal activator-repressor switching and contributes to both the activation and repression of target genes following growth factor stimulation...
A genome-wide RNAi screen reveals MAP kinase phosphatases as key ERK pathway regulators during embryonic stem cell differentiationShen Hsi Yang
Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom
PLoS Genet 8:e1003112. 2012....
The ETS transcription factors ELK1 and GABPA regulate different gene networks to control MCF10A breast epithelial cell migrationZaneta Odrowaz
University of Manchester, Manchester, United Kingdom
PLoS ONE 7:e49892. 2012..Therefore, although ELK1 and GABPA ultimately control the same biological process, they do so by regulating different cohorts of target genes associated with cytoskeletal functions and cell migration control...
Hybridization array technology coupled with chemostat culture: Tools to interrogate gene expression in Saccharomyces cerevisiaeAndrew Hayes
School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester, M13 9PT, United Kingdom
Methods 26:281-90. 2002..We use two experimental examples to illustrate the advantages of using this approach and then describe a specific application of this approach to investigate the effect of carbon and nitrogen limitation at the transcriptome level...
PIAS proteins and transcriptional regulation--more than just SUMO E3 ligases?Andrew D Sharrocks
Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
Genes Dev 20:754-8. 2006
MAP kinase phosphorylation-dependent activation of Elk-1 leads to activation of the co-activator p300Qi jing Li
Department of Cell Biology and Neuroscience, University of California, Riverside, CA 92521, USA
EMBO J 22:281-91. 2003..The pre-assembly mechanism may greatly accelerate transcription activation, which is important in regulation of expression of immediate-early response genes, in particular those involved in stress responses...
Regulation of cell cycle-specific gene expression through cyclin-dependent kinase-mediated phosphorylation of the forkhead transcription factor Fkh2pAline Pic-Taylor
Institute of Cell and Molecular Biosciences, Faculty of Medical Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
Mol Cell Biol 24:10036-46. 2004..Our data therefore identify an important regulatory target for cyclin-dependent kinases in the cell cycle and further our molecular understanding of the key cell cycle regulatory transcription factor Fkh2p...
Modern approaches in studying gene expressionAndrew D Sharrocks
Methods 26:215-6. 2002
Regulation of transcription of the RNA splicing factor hSlu7 by Elk-1 and Sp1 affects alternative splicingMoti Alberstein
Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
RNA 13:1988-99. 2007..Our results provide indications of a complex transcription regulation mechanism that controls the spatial and temporal expression of Slu7, presumably allowing regulation of tissue-specific alternative splicing events...
