title: N52 monodeamidated Bcl‑xL shows impaired oncogenic properties in vivo and in vitro.
abstract: Bcl-xL is a member of the Bcl-2 family, playing a critical role in the survival of tumor cells. Here, we show that Bcl-xL 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-xL 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-xL 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, Asp52Bcl-xL remains phosphorylatable, and thus is still an eligible target of anti-neoplasic agents. Altogether our results complement the existing data on Bcl-xL 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-xLoncogenic functions by deamidation.
authors.affiliation: CNRS, Institut de Biochimie et de Génétique Cellulaires, UMR5095, 33077 Bordeaux, France.|Université Bordeaux Ségalen, Institut de Biochimie et de Génétique Cellulaires, UMR5095, 33077 Bordeaux, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Beaumatin
authors.affiliation: CNRS, Institut de Biochimie et de Génétique Cellulaires, UMR5095, 33077 Bordeaux, France.|Université Bordeaux Ségalen, Institut de Biochimie et de Génétique Cellulaires, UMR5095, 33077 Bordeaux, France.|EA 3842, Homéostasie Cellulaire et Pathologies, Université de Limoges, 87025 Limoges Cedex, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: El Dhaybi
authors.affiliation: CNRS, Institut de Biochimie et de Génétique Cellulaires, UMR5095, 33077 Bordeaux, France.|Université Bordeaux Ségalen, Institut de Biochimie et de Génétique Cellulaires, UMR5095, 33077 Bordeaux, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Lasserre
authors.affiliation: CNRS, Institut de Biochimie et de Génétique Cellulaires, UMR5095, 33077 Bordeaux, France.|Université Bordeaux Ségalen, Institut de Biochimie et de Génétique Cellulaires, UMR5095, 33077 Bordeaux, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Salin
authors.affiliation: INCELL Corporation, San Antonio, TX 78249, USA.
authors.forename: Mary Pat
authors.initials: MP
authors.lastname: Moyer
authors.affiliation: EA 3842, Homéostasie Cellulaire et Pathologies, Université de Limoges, 87025 Limoges Cedex, France.
authors.forename: Mireille
authors.initials: M
authors.lastname: Verdier
authors.affiliation: CNRS, Institut de Biochimie et de Génétique Cellulaires, UMR5095, 33077 Bordeaux, France.|Université Bordeaux Ségalen, Institut de Biochimie et de Génétique Cellulaires, UMR5095, 33077 Bordeaux, France.
authors.forename: Stéphen
authors.initials: S
authors.lastname: Manon
authors.affiliation: CNRS, Institut de Biochimie et de Génétique Cellulaires, UMR5095, 33077 Bordeaux, France.|Université Bordeaux Ségalen, Institut de Biochimie et de Génétique Cellulaires, UMR5095, 33077 Bordeaux, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Priault
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology; D063646:Carcinogenesis / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002642:Chick Embryo; D003641:Deamination; D064593:Heterografts; D006801:Humans; D051379:Mice; D011499:Protein Processing, Post-Translational; D051020:bcl-X Protein / Q000378:metabolism*
chemical_list: D051020:bcl-X Protein
keywords: Bcl-xL; apoptosis; autophagy; cancer; post-translational modification