The role of post-translational modifications in the dimerization between the alpha and beta splicing isoforms of Signal Transducer and Activation of Transcription 3 (STAT3) and RelA

Detalhes bibliográficos
Autor(a) principal: Pimenta, Constança Lourenço
Data de Publicação: 2024
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Texto Completo: http://hdl.handle.net/10400.5/96189
Resumo: Tese de mestrado, Biologia Molecular e Genética, 2024, Universidade de Lisboa, Faculdade de Ciências
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spelling The role of post-translational modifications in the dimerization between the alpha and beta splicing isoforms of Signal Transducer and Activation of Transcription 3 (STAT3) and RelASTAT3Modificações pós-traducionaisRelAAcumulação nuclearComplementação de fluorescência bimolecularTeses de mestrado - 2024Departamento de Biologia VegetalTese de mestrado, Biologia Molecular e Genética, 2024, Universidade de Lisboa, Faculdade de CiênciasSignal Transducer and Activation of Transcription 3 (STAT3) is a pleiotropic transcription factor that plays key roles in cell survival, differentiation, and immune response. STAT3 has over 80 additional post-translational modifications (PTMs) and 4 splicing isoforms with yet unclear stoichiometry and functions. STAT3 interacts directly with the p65 subunit of Nuclear factor kappa B (NF-κB), also known as RelA, and both pathways are closely connected, regulating similar biological phenomena. The aim of this work was to elucidate the putative role of PTMs on the subcellular localization of heterodimers formed by STAT3 proteoforms and RelA, in the absence or presence of stimulating cytokines, leukemia inhibitory factor (LIF) and tumor necrosis factor α. We first confirmed the genomic alterations that prevent STAT3 expression in a HeLa STAT3-/- cell line, recently produced in our laboratory a CRISPR/Cas9 approach. HeLa STAT3-/- cells showed impaired proliferation/migration. We then developed a series of molecular tools to analyze the interaction and dynamics of STAT3α:RelA and STAT3α:STAT3β dimers in living cells, based on Bimolecular Fluorescent Complementation assays. We used these tools as templates to produce STAT3 mutants preventing PTMs on K685, Y705 or S701 or mimicking the phosphorylation on S701. Using these tools, we observed that STAT3α and RelA form a heterodimer that shows the basal subcellular distribution of RelA/NF-κB, but the response to LIF that is typical of STAT3. The subcellular distribution of different combinations of STAT3α:STAT3β and STAT3α dimers in the presence or absence of stimuli did not show major differences. The presence of one modifiable (wild-type) STAT3 monomer was sufficient to accumulate dimers in the nucleus upon LIF stimulation. Our findings enhance our understanding of the interplay between STAT3 proteoforms and between STAT3α and NF-κB signalling and could contribute to the unravel the molecular mechanisms of several pathologies, including cancer.Herrera García, Federico, 1977-Repositório da Universidade de LisboaPimenta, Constança Lourenço202420242026-11-22T00:00:00Z2024-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10400.5/96189enginfo:eu-repo/semantics/embargoedAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T16:29:45Zoai:repositorio.ulisboa.pt:10400.5/96189Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T04:16:53.162016Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv The role of post-translational modifications in the dimerization between the alpha and beta splicing isoforms of Signal Transducer and Activation of Transcription 3 (STAT3) and RelA
title The role of post-translational modifications in the dimerization between the alpha and beta splicing isoforms of Signal Transducer and Activation of Transcription 3 (STAT3) and RelA
spellingShingle The role of post-translational modifications in the dimerization between the alpha and beta splicing isoforms of Signal Transducer and Activation of Transcription 3 (STAT3) and RelA
Pimenta, Constança Lourenço
STAT3
Modificações pós-traducionais
RelA
Acumulação nuclear
Complementação de fluorescência bimolecular
Teses de mestrado - 2024
Departamento de Biologia Vegetal
title_short The role of post-translational modifications in the dimerization between the alpha and beta splicing isoforms of Signal Transducer and Activation of Transcription 3 (STAT3) and RelA
title_full The role of post-translational modifications in the dimerization between the alpha and beta splicing isoforms of Signal Transducer and Activation of Transcription 3 (STAT3) and RelA
title_fullStr The role of post-translational modifications in the dimerization between the alpha and beta splicing isoforms of Signal Transducer and Activation of Transcription 3 (STAT3) and RelA
title_full_unstemmed The role of post-translational modifications in the dimerization between the alpha and beta splicing isoforms of Signal Transducer and Activation of Transcription 3 (STAT3) and RelA
title_sort The role of post-translational modifications in the dimerization between the alpha and beta splicing isoforms of Signal Transducer and Activation of Transcription 3 (STAT3) and RelA
author Pimenta, Constança Lourenço
author_facet Pimenta, Constança Lourenço
author_role author
dc.contributor.none.fl_str_mv Herrera García, Federico, 1977-
Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Pimenta, Constança Lourenço
dc.subject.por.fl_str_mv STAT3
Modificações pós-traducionais
RelA
Acumulação nuclear
Complementação de fluorescência bimolecular
Teses de mestrado - 2024
Departamento de Biologia Vegetal
topic STAT3
Modificações pós-traducionais
RelA
Acumulação nuclear
Complementação de fluorescência bimolecular
Teses de mestrado - 2024
Departamento de Biologia Vegetal
description Tese de mestrado, Biologia Molecular e Genética, 2024, Universidade de Lisboa, Faculdade de Ciências
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024-01-01T00:00:00Z
2026-11-22T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.5/96189
url http://hdl.handle.net/10400.5/96189
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/embargoedAccess
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dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
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instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
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reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
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repository.mail.fl_str_mv info@rcaap.pt
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