Special Issue "Regulation of Apoptosis by the Bcl-2 Family of Proteins"

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Signaling and Regulated Cell Death".

Deadline for manuscript submissions: 31 January 2020.

Special Issue Editor

Prof. Alexey S. Ladokhin
E-Mail Website
Guest Editor
Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, Kansas City, Kansas 66160-7421, USA
Interests: protein–membrane interactions; Bcl-2 proteins; regulation of apoptosis; conformational switching; cancer
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

The critical step in triggering apoptosis is the permeabilization of the mitochondrial outer membrane (MOMP), which is controlled and executed by the numerous proteins of Bcl-2 family. In spite of the recent advances in solving the structures of the soluble conformations, the exact mechanism of Bcl-2 proteins remains unresolved, primarily because the functionally-important conformations are induced by interactions with the membrane. A major knowledge gap is the lack of accurate molecular pictures of protein–protein and protein–lipid interactions mediating MOMP. This Special Issue seeks reviews and original papers, both experimental and computational, covering a wide range of topics related to structure–function relationships of Bcl-2 proteins, their role in various disorders and their potentials as therapeutic targets.

Prof. Alexey S. Ladokhin
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. Cells is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). 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

  • apoptosis
  • mitochondrial outer membrane permeabilization
  • protein-membrane interactions
  • cancer
  • Bcl-2 proteins as therapeutic targets

Published Papers (3 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Other

Open AccessArticle
HOXA9 Transcriptionally Promotes Apoptosis and Represses Autophagy by Targeting NF-κB in Cutaneous Squamous Cell Carcinoma
Cells 2019, 8(11), 1360; https://doi.org/10.3390/cells8111360 - 31 Oct 2019
Abstract
Tumor suppressor HOXA9 has been identified to promote apoptosis in cutaneous squamous cell carcinoma (cSCC). However, the mechanism of such pro-apoptotic role of HOXA9 remains obscure. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis of RNA-seq data showed that NF-κB, apoptosis and autophagy [...] Read more.
Tumor suppressor HOXA9 has been identified to promote apoptosis in cutaneous squamous cell carcinoma (cSCC). However, the mechanism of such pro-apoptotic role of HOXA9 remains obscure. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis of RNA-seq data showed that NF-κB, apoptosis and autophagy pathways are significantly regulated after HOXA9 knockdown. HOXA9 transcriptionally regulates RELA, the p65 subunit of NF-κB. Loss of HOXA9 in cSCC significantly upregulates RELA expression and thus enhances NF-κB pathway. Interestingly, RELA transcriptionally promotes not only anti-apoptotic factor BCL-XL but also autophagic genes including ATG1, ATG3, and ATG12. Our results reveal an enhanced NF-κB signaling network regulated by HOXA9, which contributes to repressed apoptosis and activated autophagy in cSCC development and may represent an intervention target for cSCC therapy. Full article
(This article belongs to the Special Issue Regulation of Apoptosis by the Bcl-2 Family of Proteins)
Show Figures

Graphical abstract

Open AccessArticle
The Deubiquitinating Enzyme Inhibitor PR-619 Enhances the Cytotoxicity of Cisplatin via the Suppression of Anti-Apoptotic Bcl-2 Protein: In Vitro and In Vivo Study
Cells 2019, 8(10), 1268; https://doi.org/10.3390/cells8101268 - 17 Oct 2019
Abstract
After chemotherapy for the treatment of metastatic bladder urothelial carcinoma (UC), most patients inevitably encounter drug resistance and resultant treatment failure. Deubiquitinating enzymes (DUBs) remove ubiquitin from target proteins and play a critical role in maintaining protein homeostasis. This study investigated the antitumor [...] Read more.
After chemotherapy for the treatment of metastatic bladder urothelial carcinoma (UC), most patients inevitably encounter drug resistance and resultant treatment failure. Deubiquitinating enzymes (DUBs) remove ubiquitin from target proteins and play a critical role in maintaining protein homeostasis. This study investigated the antitumor effect of PR-619, a DUBs inhibitor, in combination with cisplatin, for bladder UC treatment. Our results showed that PR-619 effectively induced dose- and time-dependent cytotoxicity, apoptosis, and ER-stress related apoptosis in human UC (T24 and BFTC-905) cells. Additionally, co-treatment of PR-619 with cisplatin potentiated cisplatin-induced cytotoxicity in UC cells and was accompanied by the concurrent suppression of Bcl-2. We also proved that Bcl-2 overexpression is related to the chemo-resistant status in patients with metastatic UC by immunohistochemistry (IHC) staining. In a xenograft mice model, we confirmed that PR-619 enhanced the antitumor effect of cisplatin on cisplatin-naïve and cisplatin-resistant UCs. Our results demonstrated that PR-619 effectively enhanced the cisplatin-induced antitumor effect via concurrent suppression of the Bcl-2 level. These findings provide promising insight for developing a therapeutic strategy for UC treatment. Full article
(This article belongs to the Special Issue Regulation of Apoptosis by the Bcl-2 Family of Proteins)
Show Figures

Figure 1

Other

Jump to: Research

Open AccessPerspective
The Incomplete Puzzle of the BCL2 Proteins
Cells 2019, 8(10), 1176; https://doi.org/10.3390/cells8101176 - 29 Sep 2019
Abstract
The proteins of the BCL2 family are key players in multiple cellular processes, chief amongst them being the regulation of mitochondrial integrity and apoptotic cell death. These proteins establish an intricate interaction network that expands both the cytosol and the surface of organelles [...] Read more.
The proteins of the BCL2 family are key players in multiple cellular processes, chief amongst them being the regulation of mitochondrial integrity and apoptotic cell death. These proteins establish an intricate interaction network that expands both the cytosol and the surface of organelles to dictate the cell fate. The complexity and unpredictability of the BCL2 interactome resides in the large number of family members and of interaction surfaces, as well as on their different behaviours in solution and in the membrane. Although our current structural knowledge of the BCL2 proteins has been proven therapeutically relevant, the precise structure of membrane-bound complexes and the regulatory effect that membrane lipids exert over these proteins remain key questions in the field. Here, we discuss the complexity of BCL2 interactome, the new insights, and the black matter in the field. Full article
(This article belongs to the Special Issue Regulation of Apoptosis by the Bcl-2 Family of Proteins)
Show Figures

Figure 1

Back to TopTop