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Special Issue "Advances in Bcl-xL Research"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 October 2019).

Special Issue Editor

Dr. Muriel Priault
E-Mail Website
Guest Editor
UMR CNRS 5095, I.B.G.C, Université de Bordeaux, 1 Rue Camille Saint Saëns, 33077 Bordeaux Cedex, France
Interests: survival; aging; apoptosis; tumorigenesis; autophagy; deamidation; membrane protein structure

Special Issue Information

Dear Colleagues,

The oncogene Bcl-xL is an anti-apoptotic member of the Bcl-2 family that was established as a major survival factor in erythroid lineage and neuronal cells. More recently, Bcl-xL also emerged as being responsible for the resistance of malignant tumor cells to anti-cancer treatments. Over the last decade, refined description of its regulation revealed that several mechanisms are at work that make Bcl-xL instrumental in the control of survival, proliferation, and differentiation. These mechanisms comprise post-translational modifications, the dynamic interactions this protein establishes with its target membranes, and also its interactions with binding partners within and outside the Bcl-2 family of proteins. This Special Issue of IJMS will focus on how Bcl-xL is regulated at the protein level, its organization in the membrane, the plasticity of its interactome, and how it warrants a diversity of cellular functions controlled by Bcl-xL in physiology and pathology. Articles submitted can either provide a review of specific points of the literature, or be original works offering significant advances in the structure and functions of Bcl-xL.

Dr. Muriel Priault
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Survival, proliferation, and differentiation
  • Mechanisms of tumor progression
  • Mitochondria/endoplasmic reticulum interplay
  • Membrane insertion/protein oligomerization
  • Targeted drug design

Published Papers (4 papers)

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Research

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Open AccessArticle
Alpha-Tocotrienol Prevents Oxidative Stress-Mediated Post-Translational Cleavage of Bcl-xL in Primary Hippocampal Neurons
Int. J. Mol. Sci. 2020, 21(1), 220; https://doi.org/10.3390/ijms21010220 - 28 Dec 2019
Abstract
B-cell lymphoma-extra large (Bcl-xL) is an anti-apoptotic member of the Bcl2 family of proteins, which supports neurite outgrowth and neurotransmission by improving mitochondrial function. During excitotoxic stimulation, however, Bcl-xL undergoes post-translational cleavage to ∆N-Bcl-xL, and accumulation of ∆N-Bcl-xL causes mitochondrial dysfunction and neuronal [...] Read more.
B-cell lymphoma-extra large (Bcl-xL) is an anti-apoptotic member of the Bcl2 family of proteins, which supports neurite outgrowth and neurotransmission by improving mitochondrial function. During excitotoxic stimulation, however, Bcl-xL undergoes post-translational cleavage to ∆N-Bcl-xL, and accumulation of ∆N-Bcl-xL causes mitochondrial dysfunction and neuronal death. In this study, we hypothesized that the generation of reactive oxygen species (ROS) during excitotoxicity leads to formation of ∆N-Bcl-xL. We further proposed that the application of an antioxidant with neuroprotective properties such as α-tocotrienol (TCT) will prevent ∆N-Bcl-xL-induced mitochondrial dysfunction via its antioxidant properties. Primary hippocampal neurons were treated with α-TCT, glutamate, or a combination of both. Glutamate challenge significantly increased cytosolic and mitochondrial ROS and ∆N-Bcl-xL levels. ∆N-Bcl-xL accumulation was accompanied by intracellular ATP depletion, loss of mitochondrial membrane potential, and cell death. α-TCT prevented loss of mitochondrial membrane potential in hippocampal neurons overexpressing ∆N-Bcl-xL, suggesting that ∆N-Bcl-xL caused the loss of mitochondrial function under excitotoxic conditions. Our data suggest that production of ROS is an important cause of ∆N-Bcl-xL formation and that preventing ROS production may be an effective strategy to prevent ∆N-Bcl-xL-mediated mitochondrial dysfunction and thus promote neuronal survival. Full article
(This article belongs to the Special Issue Advances in Bcl-xL Research)
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Open AccessArticle
Improved Electrophoretic Separation to Assist the Monitoring of Bcl-xL Post-Translational Modifications
Int. J. Mol. Sci. 2019, 20(22), 5571; https://doi.org/10.3390/ijms20225571 - 08 Nov 2019
Abstract
Bcl-xL is an oncogene of which the survival functions are finely tuned by post-translational modifications (PTM). Within the Bcl-2 family of proteins, Bcl-xL shows unique eligibility to deamidation, a time-related spontaneous reaction. Deamidation is still a largely overlooked PTM due to [...] Read more.
Bcl-xL is an oncogene of which the survival functions are finely tuned by post-translational modifications (PTM). Within the Bcl-2 family of proteins, Bcl-xL shows unique eligibility to deamidation, a time-related spontaneous reaction. Deamidation is still a largely overlooked PTM due to a lack of easy techniques to monitor Asn→Asp/IsoAsp conversions or Glu→Gln conversions. Being able to detect PTMs is essential to achieve a comprehensive description of all the regulatory mechanisms and functions a protein can carry out. Here, we report a gel composition improving the electrophoretic separation of deamidated forms of Bcl-xL generated either by mutagenesis or by alkaline treatment. Importantly, this new gel formulation proved efficient to provide the long-sought evidence that even doubly-deamidated Bcl-xL remains eligible for regulation by phosphorylation. Full article
(This article belongs to the Special Issue Advances in Bcl-xL Research)
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Review

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Open AccessReview
BCL-xL, a Mitochondrial Protein Involved in Successful Aging: From C. elegans to Human Centenarians
Int. J. Mol. Sci. 2020, 21(2), 418; https://doi.org/10.3390/ijms21020418 - 09 Jan 2020
Abstract
B-Cell Lymphoma-extra-large (BCL-xL) is involved in longevity and successful aging, which indicates a role for BCL-xL in cell survival pathway regulation. Beyond its well described role as an inhibitor of apoptosis by preventing cytochrome c release, BCL-xL has also been related, indirectly, to [...] Read more.
B-Cell Lymphoma-extra-large (BCL-xL) is involved in longevity and successful aging, which indicates a role for BCL-xL in cell survival pathway regulation. Beyond its well described role as an inhibitor of apoptosis by preventing cytochrome c release, BCL-xL has also been related, indirectly, to autophagy and senescence pathways. Although in these latter cases, BCL-xL has dual roles, either activating or inhibiting, depending on the cell type and the specific conditions. Taken together, all these findings suggest a precise mechanism of action for BCL-xL, able to regulate the crosstalk between apoptosis, autophagy, and senescence, thus promoting cell survival or cell death. All three pathways can be both beneficial or detrimental depending on the circumstances. Thus, targeting BCL-xL would in turn be a “double-edge sword” and therefore, additional studies are needed to better comprehend this dual and apparently contradictory role of BCL-XL in longevity. Full article
(This article belongs to the Special Issue Advances in Bcl-xL Research)
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Open AccessReview
The Structural Biology of Bcl-xL
Int. J. Mol. Sci. 2019, 20(9), 2234; https://doi.org/10.3390/ijms20092234 - 07 May 2019
Cited by 3
Abstract
Interactions between the pro-survival and pro-apoptotic members of the Bcl-2 family of proteins dictate whether a cell lives or dies. Much of our knowledge of the molecular details of these interactions has come from biochemical and structural studies on the pro-survival protein Bcl-x [...] Read more.
Interactions between the pro-survival and pro-apoptotic members of the Bcl-2 family of proteins dictate whether a cell lives or dies. Much of our knowledge of the molecular details of these interactions has come from biochemical and structural studies on the pro-survival protein Bcl-xL. The first high-resolution structure of any Bcl-2 family member was of Bcl-xL, which revealed the conserved topology amongst all family members. Subsequent structures of Bcl-xL complexes with pro-apoptotic ligands demonstrated the general features of all pro-survival:pro-apoptotic complexes. Structural studies involving Bcl-xL were also the basis for the discovery of the first small-molecule pro-survival protein inhibitors, leading ultimately to the development of a new class of drugs now successfully used for cancer treatment in the clinic. This article will review our current knowledge of the structural biology of Bcl-xL and how this has impacted our understanding of the molecular details of the intrinsic apoptotic pathway. Full article
(This article belongs to the Special Issue Advances in Bcl-xL Research)
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