N52 monodeamidated Bcl‑x<sub>L</sub> shows impaired oncogenic properties <i>in vivo</i> and <i>in vitro</i> - Contrôle de l’Activation Cellulaire, Progression Tumorale et Résistance Thérapeutique
Article Dans Une Revue Oncotarget Année : 2016

N52 monodeamidated Bcl‑xL shows impaired oncogenic properties in vivo and in vitro

Résumé

Bcl-x$_L$ is a member of the Bcl-2 family, playing a critical role in the survival of tumor cells. Here, we show that Bcl-x$_L$ oncogenic function can be uncoupled from its anti-apoptotic activity when it is regulated by the post-translational deamidation of its Asn52. Bcl-xL activity can be regulated by post-translational modifications: deamidation of Asn52 and 66 into Asp residues was reported to occur exclusively in response to DNA damage, and to cripple its anti-apoptotic activity. Our work reports for the first time the spontaneous occurrence of monodeamidated Asp52Bcl-x$_L$ in control conditions, in vivo and in vitro. In the normal and cancer cell lines tested, no less than 30% and up to 56% of Bcl-x$_L$ was singly deamidated on Asn52. Functional analyses revealed that singly deamidated Bcl-xL retains anti-apoptotic functions, and exhibits enhanced autophagic activity while harboring impaired clonogenic and tumorigenic properties compared to native Bcl-xL. Additionally, Asp$^{52}$Bcl-x$_L$ remains phosphorylatable, and thus is still an eligible target of anti-neoplasic agents. Altogether our results complement the existing data on Bcl-x$_L$ deamidation: they challenge the common acceptance that Asn52 and Asn66 are equally eligible for deamidation, and provide a valuable improvement of our knowledge on the regulation of Bcl-x$_L$ oncogenic functions by deamidation.
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Dates et versions

hal-02484580 , version 1 (24-09-2024)

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Florian Beaumatin, Mohamad El Dhaybi, Jean-Paul Lasserre, Bénédicte Salin, Mary Pat Moyer, et al.. N52 monodeamidated Bcl‑xL shows impaired oncogenic properties in vivo and in vitro. Oncotarget, 2016, 7 (13), pp.17129-17143. ⟨10.18632/oncotarget.7938⟩. ⟨hal-02484580⟩
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