<> <http://www.w3.org/2000/01/rdf-schema#comment> "The repository administrator has not yet configured an RDF license."^^<http://www.w3.org/2001/XMLSchema#string> . <> <http://xmlns.com/foaf/0.1/primaryTopic> <https://discovery.ucl.ac.uk/id/eprint/19000> . <https://discovery.ucl.ac.uk/id/eprint/19000> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/Thesis> . <https://discovery.ucl.ac.uk/id/eprint/19000> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/Article> . <https://discovery.ucl.ac.uk/id/eprint/19000> <http://purl.org/dc/terms/title> "A functional RNAi screen for regulators of the serum response factor (SRF)"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/eprint/19000> <http://purl.org/ontology/bibo/abstract> "Serum response factor (SRF) controls transcription of numerous immediate early\r\nand muscle-specific genes by its association with diverse co-activators. Amongst the\r\nSRF binding regulators are the TCF family proteins, including Elk1, SAP1 and SAP2\r\nand the myocardin-related transcription factor (MRTF) family proteins including MAL\r\nand MAL16. Both types of transcriptional coactivators form a complex with SRF,\r\nwhich binds to serum response elements (SREs) upon serum activation by different\r\nupstream signal transduction pathways. While SRF activation by TCFs occur through\r\nthe MAP kinase pathway, MRTFs regulate SRF specifically through the RhoA\r\npathway.\r\nMAL, a G-actin binding protein, continuously shuttles between cytoplasm and\r\nnucleus in many unstimulated cells and appears cytoplasmic. Upon RhoA-induced actin\r\npolymerization, MAL nuclear export is blocked due to disruption of the MAL-actin\r\ninteraction. MAL accumulates in the nucleus where it binds to SRF, which results in\r\ntarget gene expression.\r\nAlthough many of the pathway components are already known, it is probable that\r\nthere are still uncharacterized factors that regulate SRF. Therefore this thesis addresses\r\nthe identification of new regulators of SRF that are specifically dependent on the RhoA\r\npathway.\r\nSince the interaction of MAL with SRF and actin represents an evolutionarily\r\nconserved regulatory mechanism between Drosophila and human and the Drosophila\r\ngenome lacks much of the genetic redundancy observed in human, a genome-wide\r\nRNA interference (RNAi) screen in cultured Drosophila cells was performed to identify\r\nkey regulators of SRF.\r\nUsing RNAi, 295 proteins in Drosophila cells were identified, of which 50 were\r\nfurther validated in human cells. Amongst the final confirmed hits, eukaryotic\r\nelongation translation factor (eEF1A) was a promising regulator for RhoA induced SRF\r\nactivation. eEF1A2 was shown to interact with MAL and depletion of eEF1A2 in\r\nunstimulated cells led to nuclear accumulation of MAL, suggesting its role as a MAL\r\nregulator. Potential roles of the remaining hits confirmed in the rescreen are also\r\ndiscussed in this thesis."^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/eprint/19000> <http://purl.org/dc/terms/date> "2009-12" . <https://discovery.ucl.ac.uk/id/org/ext-a64c3df5861c6582807add1abaadf2af> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Organization> . <https://discovery.ucl.ac.uk/id/org/ext-a64c3df5861c6582807add1abaadf2af> <http://xmlns.com/foaf/0.1/name> "UCL (University College London)"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/eprint/19000> <http://purl.org/dc/terms/issuer> <https://discovery.ucl.ac.uk/id/org/ext-a64c3df5861c6582807add1abaadf2af> . <https://discovery.ucl.ac.uk/id/eprint/19000> <http://purl.org/ontology/bibo/status> <http://purl.org/ontology/bibo/status/unpublished> . <https://discovery.ucl.ac.uk/id/eprint/19000> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-a7d7366c1ca31fa330c16c372e8da455> . <https://discovery.ucl.ac.uk/id/eprint/19000> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/19000#authors> . <https://discovery.ucl.ac.uk/id/eprint/19000#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_1> <https://discovery.ucl.ac.uk/id/person/ext-a7d7366c1ca31fa330c16c372e8da455> . <https://discovery.ucl.ac.uk/id/person/ext-a7d7366c1ca31fa330c16c372e8da455> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery.ucl.ac.uk/id/person/ext-a7d7366c1ca31fa330c16c372e8da455> <http://xmlns.com/foaf/0.1/givenName> "T."^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-a7d7366c1ca31fa330c16c372e8da455> <http://xmlns.com/foaf/0.1/familyName> "Grüner"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-a7d7366c1ca31fa330c16c372e8da455> <http://xmlns.com/foaf/0.1/name> "T. Grüner"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/eprint/19000> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://eprints.org/ontology/EPrint> . <https://discovery.ucl.ac.uk/id/eprint/19000> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://eprints.org/ontology/ThesisEPrint> . <https://discovery.ucl.ac.uk/id/eprint/19000> <http://purl.org/dc/terms/isPartOf> <https://discovery.ucl.ac.uk/id/repository> . <https://discovery.ucl.ac.uk/id/eprint/19000> <http://www.w3.org/2000/01/rdf-schema#seeAlso> <https://discovery.ucl.ac.uk/id/eprint/19000/> . <https://discovery.ucl.ac.uk/id/eprint/19000/> <http://purl.org/dc/elements/1.1/title> "HTML Summary of #19000 \n\nA functional RNAi screen for regulators of the serum response factor (SRF)\n\n" . <https://discovery.ucl.ac.uk/id/eprint/19000/> <http://purl.org/dc/elements/1.1/format> "text/html" . <https://discovery.ucl.ac.uk/id/eprint/19000/> <http://xmlns.com/foaf/0.1/primaryTopic> <https://discovery.ucl.ac.uk/id/eprint/19000> . <https://discovery.ucl.ac.uk/id/subject/16000> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://www.w3.org/2004/02/skos/core#Concept> . <https://discovery.ucl.ac.uk/id/subject/16000> <http://www.w3.org/2004/02/skos/core#prefLabel> "Off-campus Research Students"@en . <https://discovery.ucl.ac.uk/id/eprint/19000> <http://purl.org/dc/terms/subject> <https://discovery.ucl.ac.uk/id/subject/16000> .