N52 monodeamidated Bcl-x L shows impaired oncogenic properties in vivo and in vitro

Florian Beaumatin, Mohamad El Dhaybi, Jean-Paul Lasserre, Bénédicte Salin, Mary Pat Moyer, Mireille Verdier, Stéphen Manon, Muriel Priault
Oncotarget. 2016-03-06; 7(13): 17129-17143
DOI: 10.18632/oncotarget.7938

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1. Oncotarget. 2016 Mar 29;7(13):17129-43. doi: 10.18632/oncotarget.7938.

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

Beaumatin F(1)(2), El Dhaybi M(1)(2)(3), Lasserre JP(1)(2), Salin B(1)(2), Moyer
MP(4), Verdier M(3), Manon S(1)(2), Priault M(1)(2).

Author information:
(1)CNRS, Institut de Biochimie et de Génétique Cellulaires, UMR5095, 33077
Bordeaux, France.
(2)Université Bordeaux Ségalen, Institut de Biochimie et de Génétique
Cellulaires, UMR5095, 33077 Bordeaux, France.
(3)EA 3842, Homéostasie Cellulaire et Pathologies, Université de Limoges, 87025
Limoges Cedex, France.
(4)INCELL Corporation, San Antonio, TX 78249, USA.

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.

DOI: 10.18632/oncotarget.7938
PMCID: PMC4941376
PMID: 26958941 [Indexed for MEDLINE]

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