BCL‐2‐family protein tBID can act as a BAX‐like effector of apoptosis

Flores‐Romero, Hector; Hohorst, Lisa; John, M. Dwyer; Albert, Marie‐Christine; King, Louise; Beckmann, Laura; Szabó, Tamás; Hertlein, Vanessa; Luo, Xu; Villunger, Andreas; Frenzel, Lukas P.; Kashkar, Hamid; García‐Sáez, Ana J.

doi:10.15252/embj.2021108690

Cited by 94 publications

(64 citation statements)

References 78 publications

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“…Furthermore, a recent study proposed that a region of BID is involved in the ability of the protein to induce MOM polarization (MOMP) independently from BID activation of BAK1 and BAX. According to this new mechanism, the region encompasses the helix α6 of BID, which is the structural equivalent of the helix α5 in BAK1 and BAX for their pore-forming activity ( Flores-Romero et al, 2022 ). The structural details of this mechanism remain unclear and need to be further investigated.…”

Section: The Bcl2 Familymentioning

confidence: 99%

Structural Details of BH3 Motifs and BH3-Mediated Interactions: an Updated Perspective

Sora

Papaleo

2022

Front. Mol. Biosci.

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Apoptosis is a mechanism of programmed cell death crucial in organism development, maintenance of tissue homeostasis, and several pathogenic processes. The B cell lymphoma 2 (BCL2) protein family lies at the core of the apoptotic process, and the delicate balance between its pro- and anti-apoptotic members ultimately decides the cell fate. BCL2 proteins can bind with each other and several other biological partners through the BCL2 homology domain 3 (BH3), which has been also classified as a possible Short Linear Motif and whose distinctive features remain elusive even after decades of studies. Here, we aim to provide an updated overview of the structural features characterizing BH3s and BH3-mediated interactions (with a focus on human proteins), elaborating on the plasticity of BCL2 proteins and the motif properties. We also discussed the implication of these findings for the discovery of interactors of the BH3-binding groove of BCL2 proteins and the design of mimetics for therapeutic purposes.

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Section: The Bcl2 Familymentioning

confidence: 99%

Structural Details of BH3 Motifs and BH3-Mediated Interactions: an Updated Perspective

Sora

Papaleo

2022

Front. Mol. Biosci.

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“…Apoptosis is a form of programmed cell death that plays a vital role in immune system regulation, homeostasis, infection, damage, and clearance of senescent cells [ 20 , 21 ]. The BCL2 antiapoptotic protein is a major regulator of the BCL2 family, which acts on the mitochondrial outer membrane to reduce the release of cytochrome C, thereby inhibiting apoptosis [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

IL-22 Protects against Biliary Ischemia-Reperfusion Injury after Liver Transplantation via Activating STAT3 and Reducing Apoptosis and Oxidative Stress Levels In Vitro and In Vivo

Bai

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Biliary complications are currently one of the leading causes of liver failure and patient death after liver transplantation and need to be solved urgently. Biliary ischemia-reperfusion injury (IRI) is one of the important causes of biliary complications. IL-22 has a protective effect on liver injury and hepatitis diseases, and its safety and efficacy in the treatment of hepatitis have also been proved in human clinical experiments. Furthermore, multiple studies have confirmed that IL-22 promotes the proliferation and repair of epithelial cells in various organs. Still, its function in the bile duct after transplantation has not been explored. This study was aimed at investigating the effects of IL-22 on cholangiocyte IRI in vitro and in vivo and exploring its underlying mechanisms. We simulated the hypoxia process of bile duct epithelial cells through in vitro experiments to investigate the protective function and molecular mechanism of IL-22 on bile duct epithelial cells. Subsequently, the function and mechanism of IL-22 in the biliary IRI model of autologous orthotopic liver transplantation in rats were assessed. This study confirmed that IL-22 could promote cholangiocyte proliferation, decrease the apoptosis rate of cholangiocytes and tissues, decrease MDA levels, and increase SOD levels by activating STAT3. In addition, IL-22 can also reduce the level of mitochondrial membrane depolarization, protect mitochondria, reduce ROS production, and play a role in protecting bile ducts. These findings provide evidence for IL-22 as a novel and effective treatment for biliary IRI after liver transplantation.

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“…Bcl-2 and Bax, members of the Bcl-2 protein family, are important cytokines that regulate apoptosis. Bcl-2 mainly inhibits apoptosis, whereas Bax promotes apoptosis [40] . When stimulated by the cell death signal, Bax can upregulate the release of apoptotic factors and induce apoptosis, whereas Bcl-2 inhibits apoptosis in this process [41] .…”

Section: Discussionmentioning

confidence: 99%

Lb-miR166a has a potentially positive impact on the treatment of kidney cancer

Zhang

Xie

et al. 2022

Preprint

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Background Renal cell carcinoma (RCC) is the seventh most common tumor worldwide. The incidence rate of RCC ranks second among urinary system tumors, and the incidence rate has been increasing in recent years. Recent studies have shown that plant miRNAs can be absorbed into organisms through diet, and can regulate target gene expression and physiological function of predators across species. As a traditional Chinese medicine, Lycium barbarum has a wide range of antitumor effects. However, there are no reports on the cross-border regulation of tumors by Lycium barbarum miRNA (Lb-miRNA). Methods Human RCC cells (Caki-1) were cultured in vitro. The overexpression group of Lb-miR166a was constructed using lentivirus transfection. The effect of Lb-miR166a on the expression of RCC cells was analyzed using transcriptome sequencing, and differentially expressed genes were screened. Combined with bioinformatics technology, the relevant mechanisms by which Lb-miR166a regulates the occurrence and development of RCC were screened and verified, and in vivo tumor-bearing experiments on nude mice verified the effect of Lb-miR166a expression on the occurrence, development, invasion, and metastasis of RCC. Results Transcriptome sequencing analysis showed that Lb-miR166a regulated the expression of a variety of genes in tumor cells and regulated a large number of signaling pathways related to tumor occurrence and development. The overall finding was that Lb-miR166a inhibited tumor cell proliferation, promoted tumor cell apoptosis, and inhibited cell invasion and metastasis. The tumor-bearing experiment in nude mice also showed that the subcutaneous tumor formation volume decreased in Lb-miR166a group mice, as did the expression of tumor cell Ki67 and the number of liver metastases. Conclusion This study explains the role of Lb-miR166a in the treatment of RCC and its underlying mechanisms. These results further improve the antitumor mechanism of L. barbarum and provide ideas for the clinical development of targeted drugs for the treatment of RCC.

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BCL‐2‐family protein tBID can act as a BAX‐like effector of apoptosis

Cited by 94 publications

References 78 publications

Structural Details of BH3 Motifs and BH3-Mediated Interactions: an Updated Perspective

Structural Details of BH3 Motifs and BH3-Mediated Interactions: an Updated Perspective

IL-22 Protects against Biliary Ischemia-Reperfusion Injury after Liver Transplantation via Activating STAT3 and Reducing Apoptosis and Oxidative Stress Levels In Vitro and In Vivo

Lb-miR166a has a potentially positive impact on the treatment of kidney cancer

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