SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer

The posttranslational modification of proteins critically influences many biological processes and is a key mechanism that regulates the function of the RNA-binding protein Hu antigen R (HuR), a hub in liver cancer. Here, we show that HuR is SUMOylated in the tumor sections of patients with hepatoce...

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Detalhes bibliográficos
Autores: Lachiondo Ortega, Sofia, Rejano Gordillo, Claudia M., Simon, Jorge, Lopitz Otsoa, Fernando, C. Delgado, Teresa, Mazan Mamczarz, Krystyna, Goikoetxea Usandizaga, Naroa, Velázquez Cruz, Alejandro, Díaz Quintana, Antonio Jesús, Díaz Moreno, Irene, Martínez-Chantar, María Luz
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Recursos:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/160902
Acesso em linha:https://hdl.handle.net/11441/160902
https://doi.org/10.1016/j.celrep.2024.113924
Access Level:acceso abierto
Palavra-chave:CP: Cancer
CP: Molecular biology
ELAVL1
HCC
PTMs
Senescence
SUMO
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repository_id_str
spelling SUMOylation controls Hu antigen R posttranscriptional activity in liver cancerLachiondo Ortega, SofiaRejano Gordillo, Claudia M.Simon, JorgeLopitz Otsoa, FernandoC. Delgado, TeresaMazan Mamczarz, KrystynaGoikoetxea Usandizaga, NaroaVelázquez Cruz, AlejandroDíaz Quintana, Antonio JesúsDíaz Moreno, IreneMartínez-Chantar, María LuzCP: CancerCP: Molecular biologyELAVL1HCCPTMsSenescenceSUMOThe posttranslational modification of proteins critically influences many biological processes and is a key mechanism that regulates the function of the RNA-binding protein Hu antigen R (HuR), a hub in liver cancer. Here, we show that HuR is SUMOylated in the tumor sections of patients with hepatocellular carcinoma in contrast to the surrounding tissue, as well as in human cell line and mouse models of the disease. SUMOylation of HuR promotes major cancer hallmarks, namely proliferation and invasion, whereas the absence of HuR SUMOylation results in a senescent phenotype with dysfunctional mitochondria and endoplasmic reticulum. Mechanistically, SUMOylation induces a structural rearrangement of the RNA recognition motifs that modulates HuR binding affinity to its target RNAs, further modifying the transcriptomic profile toward hepatic tumor progression. Overall, SUMOylation constitutes a mechanism of HuR regulation that could be potentially exploited as a therapeutic strategy for liver cancer.Ministerio de Ciencia e Innovación PID2020-117116RB-I00, RTC2019-007125-1, RED2022-134397-T, PID2019-104878RB-I00, PID2020-114178GB-I00, PID2022-136788OB-I00,Instituto de Salud Carlos III DTS20/ 00138, PI19/ 00819, PI20/01301, PI18/ 01075, CPII19/00008, PI21/00922Fundación la Caixa HR17-00601Consejo Nacional de Ciencia y Tecnología (CONACYT). México 0280365European Union 765445, 804236, 825510National Institutes of Health (NIH). United States Z01-AG000511-23Junta de Andalucía BIO-198, US-1254317, P18-FR-3487, P18-HO-4091Junta de Castilla y León SA063P17Gobierno de Navarra GºNa 42/21Gobierno Vasco 2019222054, 2020333010, 2021333003, KK-2020/00008National Cancer Institute (NCI), NIH. United States R37CA230636ElsevierBioquímica Vegetal y Biología MolecularMinisterio de Ciencia e Innovación (MICIN). EspañaInstituto de Salud Carlos IIIFundación la CaixaConsejo Nacional de Ciencia y Tecnología (CONACYT). MéxicoEuropean Union (UE)National Institutes of Health. United StatesJunta de AndalucíaJunta de Castilla-LeónGobierno de NavarraGobierno VascoNational Cancer Institute (NCI), NIH. United States2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/160902https://doi.org/10.1016/j.celrep.2024.113924reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésCell Reports, 43 (3), 113924.PID2020-117116RB-I00RTC2019-007125-1RED2022-134397-TPID2019-104878RB-I00PID2020-114178GB-I00PID2022-136788OB-I00DTS20/ 00138PI19/ 00819PI20/01301PI18/ 01075CPII19/00008PI21/00922HR17-006010280365765445804236825510Z01-AG000511-23BIO-198US-1254317P18-FR-3487P18-HO-4091SA063P17GºNa 42/21201922205420203330102021333003KK-2020/00008R37CA230636https://doi.org/10.1016/j.celrep.2024.113924info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1609022026-06-17T12:51:07Z
dc.title.none.fl_str_mv SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer
title SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer
spellingShingle SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer
Lachiondo Ortega, Sofia
CP: Cancer
CP: Molecular biology
ELAVL1
HCC
PTMs
Senescence
SUMO
title_short SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer
title_full SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer
title_fullStr SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer
title_full_unstemmed SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer
title_sort SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer
dc.creator.none.fl_str_mv Lachiondo Ortega, Sofia
Rejano Gordillo, Claudia M.
Simon, Jorge
Lopitz Otsoa, Fernando
C. Delgado, Teresa
Mazan Mamczarz, Krystyna
Goikoetxea Usandizaga, Naroa
Velázquez Cruz, Alejandro
Díaz Quintana, Antonio Jesús
Díaz Moreno, Irene
Martínez-Chantar, María Luz
author Lachiondo Ortega, Sofia
author_facet Lachiondo Ortega, Sofia
Rejano Gordillo, Claudia M.
Simon, Jorge
Lopitz Otsoa, Fernando
C. Delgado, Teresa
Mazan Mamczarz, Krystyna
Goikoetxea Usandizaga, Naroa
Velázquez Cruz, Alejandro
Díaz Quintana, Antonio Jesús
Díaz Moreno, Irene
Martínez-Chantar, María Luz
author_role author
author2 Rejano Gordillo, Claudia M.
Simon, Jorge
Lopitz Otsoa, Fernando
C. Delgado, Teresa
Mazan Mamczarz, Krystyna
Goikoetxea Usandizaga, Naroa
Velázquez Cruz, Alejandro
Díaz Quintana, Antonio Jesús
Díaz Moreno, Irene
Martínez-Chantar, María Luz
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Bioquímica Vegetal y Biología Molecular
Ministerio de Ciencia e Innovación (MICIN). España
Instituto de Salud Carlos III
Fundación la Caixa
Consejo Nacional de Ciencia y Tecnología (CONACYT). México
European Union (UE)
National Institutes of Health. United States
Junta de Andalucía
Junta de Castilla-León
Gobierno de Navarra
Gobierno Vasco
National Cancer Institute (NCI), NIH. United States
dc.subject.none.fl_str_mv CP: Cancer
CP: Molecular biology
ELAVL1
HCC
PTMs
Senescence
SUMO
topic CP: Cancer
CP: Molecular biology
ELAVL1
HCC
PTMs
Senescence
SUMO
description The posttranslational modification of proteins critically influences many biological processes and is a key mechanism that regulates the function of the RNA-binding protein Hu antigen R (HuR), a hub in liver cancer. Here, we show that HuR is SUMOylated in the tumor sections of patients with hepatocellular carcinoma in contrast to the surrounding tissue, as well as in human cell line and mouse models of the disease. SUMOylation of HuR promotes major cancer hallmarks, namely proliferation and invasion, whereas the absence of HuR SUMOylation results in a senescent phenotype with dysfunctional mitochondria and endoplasmic reticulum. Mechanistically, SUMOylation induces a structural rearrangement of the RNA recognition motifs that modulates HuR binding affinity to its target RNAs, further modifying the transcriptomic profile toward hepatic tumor progression. Overall, SUMOylation constitutes a mechanism of HuR regulation that could be potentially exploited as a therapeutic strategy for liver cancer.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/160902
https://doi.org/10.1016/j.celrep.2024.113924
url https://hdl.handle.net/11441/160902
https://doi.org/10.1016/j.celrep.2024.113924
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Cell Reports, 43 (3), 113924.
PID2020-117116RB-I00
RTC2019-007125-1
RED2022-134397-T
PID2019-104878RB-I00
PID2020-114178GB-I00
PID2022-136788OB-I00
DTS20/ 00138
PI19/ 00819
PI20/01301
PI18/ 01075
CPII19/00008
PI21/00922
HR17-00601
0280365
765445
804236
825510
Z01-AG000511-23
BIO-198
US-1254317
P18-FR-3487
P18-HO-4091
SA063P17
GºNa 42/21
2019222054
2020333010
2021333003
KK-2020/00008
R37CA230636
https://doi.org/10.1016/j.celrep.2024.113924
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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