Results 1 to 10 of about 153,102 (279)

MDM2-BCL-XL PROTACs enable degradation of BCL-XL and stabilization of p53

Acta Materia Medica, 2022
Inhibition or degradation of the anti-apoptotic protein BCL-XL is a viable strategy for cancer treatment. Despite the recent development of PROTACs for degradation of BCL-XL, the choice of E3 ligase has been restricted to VHL and CRBN.
Mengyang Chang, Feng Gao, Jing Chen, Giri Gnawali, Wei Wang   +4 more
doaj   +3 more sources

Bcl-XL inhibits membrane permeabilization by competing with Bax. [PDF]

PLoS Biology, 2008
Although Bcl-XL and Bax are structurally similar, activated Bax forms large oligomers that permeabilize the outer mitochondrial membrane, thereby committing cells to apoptosis, whereas Bcl-XL inhibits this process. Two different models of Bcl-XL function
Lieven P Billen, Candis L Kokoski, Jonathan F Lovell, Brian Leber, David W Andrews   +4 more
doaj   +2 more sources

Allosteric regulation of BH3-in-groove interactions by tail anchors of BCL-xL complexes limits BH3 mimetic antagonism [PDF]

Nature Communications
BCL-xL promotes cell survival by binding BH3-only initiators through its hydrophobic groove. Combining resonance energy transfer assays and molecular dynamics simulations, we unravel that membrane anchoring of BCL-xL via its tail anchor selectively ...
Laurent Maillet, Aurélie Fétiveau, Lisenn Lalier, Nena Martin, Sophie Barillé-Nion, Catherine Guette, Fabien Gautier, Stéphane Téletchéa, Philippe Paul Juin   +8 more
doaj   +2 more sources

Targeting BCL-XL for degradation synergizes with gemcitabine against cholangiocarcinoma [PDF]

BMC Medicine
Background Cholangiocarcinoma (CCA) remains a highly lethal malignancy with a dismal prognosis, primarily driven by therapeutic resistance. A dominant resistance mechanism involves overexpression of anti-apoptotic BCL-2 proteins (BCL-XL, BCL-2, MCL-1 ...
Qinghua Zeng, Yan Zhang, Yiwen Yang, Xin Liu, Xin Dong, Yongzhang Pan, Li Hu, Ao Zhang, Jian Yang, Qiuni Luo, Xiang Lai, Guoping Zhu, Xuan Zhang, Yonghan He   +13 more
doaj   +2 more sources

BH3 mimetics targeting BCL-XL have efficacy in solid tumors with RB1 loss and replication stress [PDF]

Nature Communications
BH3 mimetic drugs that inhibit BCL-2, BCL-XL, or MCL-1 have limited activity in solid tumors. Through assessment of xenograft-derived 3D prostate cancer models and cell lines we find that tumors with RB1 loss are sensitive to BCL-XL inhibition.
Andreas Varkaris, Keshan Wang, Mannan Nouri, Nina Kozlova, Daniel R. Schmidt, Anastasia Stavridi, Seiji Arai, Nicholas Ambrosio, Larysa Poluben, Juan M. Jimenez-Vacas, Daniel Westaby, Juliet Carmichael, Fang Xie, Ines Figueiredo, Lorenzo Buroni, Antje Neeb, Bora Gurel, Nicholas Chevalier, Lisha Brown, Olga Voznesensky, Shao-Yong Chen, Joshua W. Russo, Xin Yuan, Dejan Juric, Himisha Beltran, Johann S. De Bono, Matthew G. Vander Heiden, David J. Einstein, Taru Muranen, Eva Corey, Adam Sharp, Steven P. Balk   +31 more
doaj   +2 more sources

Evaluation of Bak and Bcl-Xl gene expression among pediatric patients with acute primary immune thrombocytopenia [PDF]

Clinical and Experimental Pediatrics
Background Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by a low platelet counts and an increased risk of bleeding. Moreover, the apoptotic mechanisms of platelets may influence their production and lifespan.
Amira Zaki Badawy, Samia Hassan Kandel, Iman Aly Ahmedy, Mahmoud Ahmed Elhawy, Sally Mohamed El-Hefnawy, Dina Fouad Sief El-Nasr Zidan, Hanan Hassan El-sheity   +6 more
doaj   +2 more sources

Oxidative stress battles neuronal Bcl-xL in a fight to the death

Neural Regeneration Research, 2021
Bcl-xL is a pro-survival protein of the Bcl2 family found in the mitochondrial membrane. Bcl-xL supports growth, development, and maturation of neurons, and it also prevents neuronal death during neurotoxic stimulation.
Han-A Park, Katheryn Broman, Elizabeth A Jonas   +2 more
doaj   +1 more source

Bcl-xL Is Required by Primary Hippocampal Neurons during Development to Support Local Energy Metabolism at Neurites

Biology, 2021
B-cell lymphoma-extra large (Bcl-xL) is a mitochondrial protein known to inhibit mitochondria-dependent intrinsic apoptotic pathways. An increasing number of studies have demonstrated that Bcl-xL is critical in regulating neuronal energy metabolism and ...
Joseph Jansen, Madison Scott, Emma Amjad, Allison Stumpf, Kimberly H. Lackey, Kim A. Caldwell, Han-A Park   +6 more
doaj   +1 more source

Ser14 phosphorylation of Bcl-xL mediates compensatory cardiac hypertrophy in male mice

Nature Communications, 2023
The anti-apoptotic function of Bcl-xL in the heart during ischemia/reperfusion is diminished by K-Ras-Mst1-mediated phosphorylation of Ser14, which allows dissociation of Bcl-xL from Bax and promotes cardiomyocyte death.
Michinari Nakamura, Mariko Aoyagi Keller, Nadezhda Fefelova, Peiyong Zhai, Tong Liu, Yimin Tian, Shohei Ikeda, Dominic P. Del Re, Hong Li, Lai-Hua Xie, Junichi Sadoshima   +10 more
doaj   +1 more source

Anti‐apoptotic protein BCL‐XL as a therapeutic vulnerability in gastric cancer

Animal Models and Experimental Medicine, 2023
Background New therapeutic targets are needed to improve the outcomes for gastric cancer (GC) patients with advanced disease. Evasion of programmed cell death (apoptosis) is a hallmark of cancer cells and direct induction of apoptosis by targeting the ...
Yumin Wei, Liping Zhang, Chao Wang, Zefeng Li, Mingjie Luo, Guomin Xie, Xingjiu Yang, Mengyuan Li, Shuyue Ren, Dongbing Zhao, Ran Gao, Jia‐Nan Gong   +11 more
doaj   +1 more source