p65/RelA NF-κB fragments generated by RIPK3 activity regulate tumorigenicity, cell metabolism, and stemness characteristics.
RIPK3
cancer
fragment
p65/RelA
stemness
Journal
Journal of cellular biochemistry
ISSN: 1097-4644
Titre abrégé: J Cell Biochem
Pays: United States
ID NLM: 8205768
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
17
11
2021
received:
09
08
2021
accepted:
10
12
2021
pubmed:
21
12
2021
medline:
14
4
2022
entrez:
20
12
2021
Statut:
ppublish
Résumé
Receptor-interacting protein kinase 3 (RIPK3) can induce necroptosis, apoptosis, or cell proliferation and is silenced in several hematological malignancies. We previously reported that RIPK3 activity independent of its kinase domain induces caspase-mediated p65/RelA cleavage, resulting in N-terminal 1-361 and C-terminal 362-549 fragments. We show here that a noncleavable p65/RelA D361E mutant expressed in DA1-3b leukemia cells decreases mouse survival times and that coexpression of p65/RelA fragments increases the tumorigenicity of B16F1 melanoma cells. This aggressiveness in vivo did not correlate with NF-κB activity measured in vitro. The fragments and p65/RelA D361E mutant induced different expression profiles in DA1-3b and B16F1 cells. Stemness markers were affected: p65/RelA D361E increased ALDH activity in DA1-3b cells, and fragment expression increased melanoma sphere formation in B16/F1 cells. p65/RelA fragments and the D361E noncleavable mutant decreased oxidative or glycolytic cell metabolism, with differences observed between models. Thus, p65/RelA cleavage initiated by kinase-independent RIPK3 activity in cancer cells is not neutral and induces pleiotropic effects in vitro and in vivo that may vary across tumor types.
Identifiants
pubmed: 34927768
doi: 10.1002/jcb.30198
pmc: PMC9299825
doi:
Substances chimiques
NF-kappa B
0
Transcription Factor RelA
0
Receptor-Interacting Protein Serine-Threonine Kinases
EC 2.7.11.1
Ripk3 protein, mouse
EC 2.7.11.1
Caspases
EC 3.4.22.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
543-556Informations de copyright
© 2021 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals LLC.
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