Skip to Main content Skip to Navigation

Rôle oncogénique des fragments de p65/RelA Nf-kB générés par l'activité de RIPK3

Abstract : The 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 p65/RelA caspase-mediated cleavage resulting in N-terminal 1-362 and C-terminal 362-549 fragments. We show here that a non-cleavable p65/RelA D361E mutant expressed in DA1-3b leukemia cells decrease mouse survival and that coexpressed p65/RelA fragments increase tumoriginicty of B16/F1 melanoma cells that did not correlated with in vitro measured Nf-kB activity. Fragments and p65/RelA fragments display different expression profiles in DA1-3b leukemic cells, with the notable modulation of gene expression of the Stefin cysteine protease inhibitor family and of SLC4A5, a Na+-coupled HCO−3 transporter. DA1-3b cells expressing p65/RelA D361E mutant showed more basic intracellular pH. p65/RelA fragments induced ovexpression of PD-L1 immunoescape molecule in DA1-3b cells. Markers of stemness were also affected: p65/RelA D361E induced increased ALDH activity in DA1-3b cells and fragments expression resulted in increased melanoma sphere formation in B16/F1 cells. Thus, far from being neutral, p65/RelA cleavage initiated by kinase independent activity of RIPK3 induced a pleiotropic range of effects in vitro and in vivo in cancer cells, that may vary across tumor types.
Document type :
Complete list of metadatas

Cited literature [270 references]  Display  Hide  Download
Contributor : Abes Star :  Contact
Submitted on : Wednesday, August 29, 2018 - 5:10:06 PM
Last modification on : Tuesday, October 20, 2020 - 3:28:41 AM
Long-term archiving on: : Friday, November 30, 2018 - 4:21:19 PM


Version validated by the jury (STAR)


  • HAL Id : tel-01864360, version 1



Céline Latreche-Carton. Rôle oncogénique des fragments de p65/RelA Nf-kB générés par l'activité de RIPK3. Médecine humaine et pathologie. Université du Droit et de la Santé - Lille II, 2017. Français. ⟨NNT : 2017LIL2S048⟩. ⟨tel-01864360⟩



Record views


Files downloads