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SOAP: Signaling in Oncogenesis, Angiogenesis, and Permeability

On the ground of our interests for molecular piracy exerted by tumor cells to survive, adapt and remodel their environment, we explore the signaling mechanisms involved in non-oncogene addiction and loss of vascular homeostasis.

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Latest News

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SOAP lab turning green
 SHARPIN is Phosphorylated!
Thys et al., IScience 2020
 Preprints of the Lab
Andre-Gregoire et al., Sabbagh et al.

Research Highlights

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Paracaspase MALT1 regulates glioma cell survival by controlling endo‐lysosome homeostasis.

Kathryn A Jacobs, G André-Grégoire, C Maghe, A Thys, Y Li, E Harford-Wright, K Trillet, T Douanne, C Alves-Nicolau, JS Frénel, N Bidère, J Gavard.

EMBO Journal 2019

 

This study unveils that the paracaspase activity of MALT1, which was previously linked to antigen receptor‐mediated NF‐κB activation and lymphomas, is decisive for the expansion of glioblastoma stem‐like cells (GSC), highlighting potential therapeutic strategies against brain cancers.

i) Expression and catalytic activity of MALT1 are required for GSC expansion. ii) Pharmacological targeting of MALT1 is lethal to GSCs and reduces the expansion of established tumors in mice. iii) MALT1 depletion results in an increased endo‐lysosomal compartment and decreased mTOR signaling. iv) MALT1 expression negatively correlates to that of RNA‐binding protein Quaking to control endo‐lysosomal biogenesis.

Capture d’écran 2020-12-14 à 21.20.58.

Serine 165 Phosphorylation of SHARPIN regulates the Activation of NF-κB.

Thys A, Trillet K, Rosinska S, Gayraud A, Douanne T, Danger Y, Renaud CCN, Antigny L, Lavigne R, Pineau C, Com E, Vérité F, Gavard J, Bidère N.

IScience 2020

 

The adaptor SHARPIN composes, together with the E3 ligases HOIP and HOIL1, the linear ubiquitin chain assembly complex (LUBAC). This enzymatic complex catalyzes and stamps atypical linear ubiquitin chains onto substrates to modify their fate, and has been linked to the regulation of the NF-κB pathway downstream most immunoreceptors, inflammation and cell death. However, how this signaling complex is regulated is not fully understood. Here, we report that a portion of SHARPIN is constitutively phosphorylated on the serine in position 165 in lymphoblastoid cells, and can be further induced following T-cell receptor stimulation. Analysis of a phosphorylation-resistant mutant of SHARPIN revealed that this mark controls the linear ubiquitination of the NF-κB regulator NEMO, and allows the optimal activation of NF-κB in response to TNFα. These results identify an additional layer of regulation of the LUBAC, and unveil potential strategies to modulate its action.

Funding

CNRS

 

Fondation ARC

 

Fondation de France

 

Fondation pour la Recherche Médicale

Institut National du Cancer

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Inserm

Ligue Nationale et Régionale contre le Cancer

Région Pays-de-la-Loire

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