SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer.
CP: Cancer
CP: Molecular biology
ELAVL1
HCC
PTMs
SUMO
senescence
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
26 Mar 2024
26 Mar 2024
Historique:
received:
30
09
2022
revised:
08
08
2023
accepted:
21
02
2024
medline:
1
4
2024
pubmed:
20
3
2024
entrez:
20
3
2024
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 38507413
pii: S2211-1247(24)00252-3
doi: 10.1016/j.celrep.2024.113924
pmc: PMC11025316
mid: NIHMS1980936
pii:
doi:
Substances chimiques
ELAV-Like Protein 1
0
RNA
63231-63-0
Elavl1 protein, mouse
0
ELAVL1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
113924Subventions
Organisme : NCI NIH HHS
ID : R37 CA230636
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 AG000511
Pays : United States
Informations de copyright
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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