Asymmetric post-translational modifications regulate the nuclear translocation of STAT3 homodimers in response to leukemia inhibitory factor

STAT3 is a pleiotropic transcription factor overactivated in 70% of solid tumours. We have recently reported that inactivating mutations on residues susceptible to post-translational modifications (PTMs) in only one of the monomers (i.e. asymmetric) caused changes in the cellular distribution of STA...

Full description

Saved in:
Bibliographic Details
Published in:Cellular oncology (Dordrecht) 2024-06, Vol.47 (3), p.1065-1070
Main Authors: Diallo, Mickael, Pimenta, Constança, Murtinheira, Fernanda, Martins-Alves, Daniela, Pinto, Francisco R., da Costa, André Abrantes, Letra-Vilela, Ricardo, Martin, Vanesa, Rodriguez, Carmen, Rodrigues, Mário S., Herrera, Federico
Format: Article
Language:English
Subjects:
Active Transport, Cell Nucleus
Biomedical and Life Sciences
Biomedicine
Brief Report
Cancer Research
Cell Nucleus - metabolism
HeLa Cells
Humans
Leukemia Inhibitory Factor - metabolism
Oncology
Pathology
Phosphorylation
Protein Multimerization
Protein Processing, Post-Translational
Protein Transport - drug effects
STAT3 Transcription Factor - metabolism
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:STAT3 is a pleiotropic transcription factor overactivated in 70% of solid tumours. We have recently reported that inactivating mutations on residues susceptible to post-translational modifications (PTMs) in only one of the monomers (i.e. asymmetric) caused changes in the cellular distribution of STAT3 homodimers. Here, we used more controlled experimental conditions, i.e. without the interference of endogenous STAT3 (STAT3-/- HeLa cells) and in the presence of a defined cytokine stimulus (Leukemia Inhibitory Factor, LIF), to provide further evidence that asymmetric PTMs affect the nuclear translocation of STAT3 homodimers. Time-lapse microscopy for 20 min after LIF stimulation showed that S727 dephosphorylation (S727A) and K685 inactivation (K685R) slightly enhanced the nuclear translocation of STAT3 homodimers, while K49 inactivation (K49R) delayed STAT3 nuclear translocation. Our findings suggest that asymmetrically modified STAT3 homodimers could be a new level of STAT3 regulation and, therefore, a potential target for cancer therapy.
ISSN:2211-3428
2211-3436
2211-3436
DOI:10.1007/s13402-023-00911-9