The scaffold protein IQGAP1 links heat-induced stress signals to alternative splicing regulation in gastric cancer cells

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Birladeanu, Andrada Maria
• dc.contributor.author Rogalska, Malgorzata
• dc.contributor.author Potiri, Myrto
• dc.contributor.author Papadaki, Vasiliki
• dc.contributor.author Andreadou, Margarita
• dc.contributor.author Kontoyiannis, Dimitris L.
• dc.contributor.author Lewis, Joe D.
• dc.contributor.author Erpapazoglou, Zoi
• dc.contributor.author Kafasla, Panagiota
• dc.date.accessioned 2021-09-10T07:19:06Z
• dc.date.issued 2021
• dc.description.abstract In response to oncogenic signals, Alternative Splicing (AS) regulators such as SR and hnRNP proteins show altered expression levels, subnuclear distribution and/or post-translational modification status, but the link between signals and these changes remains unknown. Here, we report that a cytosolic scaffold protein, IQGAP1, performs this task in response to heat-induced signals. We show that in gastric cancer cells, a nuclear pool of IQGAP1 acts as a tethering module for a group of spliceosome components, including hnRNPM, a splicing factor critical for the response of the spliceosome to heat-shock. IQGAP1 controls hnRNPM's sumoylation, subnuclear localisation and the relevant response of the AS machinery to heat-induced stress. Genome-wide analyses reveal that IQGAP1 and hnRNPM co-regulate the AS of a cell cycle-related RNA regulon in gastric cancer cells, thus favouring the accelerated proliferation phenotype of gastric cancer cells. Overall, we reveal a missing link between stress signals and AS regulation.
• dc.description.sponsorship InfrafrontierGR/Phenotypos Infrastructure, co-funded by Greece and the European Union (European Regional Development Fund) [NSRF 2014–2020, MIS 5002135]; Hellenic Foundation for Research & Innovation (HFRI) and the General Secretariat for Research and Technology (GSRT) [grant agreement 846 to ZE]; MR was supported by the European Research Council [ERC AdvG 670146]; European Commission Grant FP7-PEOPLE-2010-IEF [274837] to PK; Stavros Niarchos Foundation (SNF) donation to BSRC “Al. Fleming”.
• dc.format.mimetype application/pdf
• dc.identifier.citation Birladeanu AM, Rogalska M, Potiri M, Papadaki V, Andreadou M, Kontoyiannis DL, Lewis JD, Erpapazoglou Z, Kafasla P. The scaffold protein IQGAP1 links heat-induced stress signals to alternative splicing regulation in gastric cancer cells. Oncogene. 2021;40:5518-32. DOI: 10.1038/s41388-021-01963-7
• dc.identifier.doi http://dx.doi.org/10.1038/s41388-021-01963-7
• dc.identifier.issn 0950-9232
• dc.identifier.uri http://hdl.handle.net/10230/48423
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Oncogene. 2021;40:5518-32
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/670146
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/274837
• dc.rights © Springer Nature Publishing AG Birladeanu AM, Rogalska M, Potiri M, Papadaki V, Andreadou M, Kontoyiannis DL, Lewis JD, Erpapazoglou Z, Kafasla P. The scaffold protein IQGAP1 links heat-induced stress signals to alternative splicing regulation in gastric cancer cells. Oncogene. 2021;40:5518-32. DOI: 10.1038/s41388-021-01963-7 [http://dx.doi.org/10.1038/s41388-021-01963-7]
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword Gastric cancer
• dc.subject.keyword RNA splicing
• dc.subject.keyword Stress signalling
• dc.title The scaffold protein IQGAP1 links heat-induced stress signals to alternative splicing regulation in gastric cancer cells
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion