Ask about this productRelated genes to: BCL2L1 Blocking Peptide
- Gene:
- BCL2L1 NIH gene
- Name:
- BCL2 like 1
- Previous symbol:
- -
- Synonyms:
- BCLX, BCL2L, Bcl-X, bcl-xL, bcl-xS, PPP1R52
- Chromosome:
- 20q11.21
- Locus Type:
- gene with protein product
- Date approved:
- 1997-10-30
- Date modifiied:
- 2016-01-13
Related products to: BCL2L1 Blocking Peptide
Related articles to: BCL2L1 Blocking Peptide
- Severe asthma is characterized by both steroid resistance and fibrotic remodeling. We hypothesized that myofibroblasts in fibrotic lung tissue acquire glucocorticoid resistance through the upregulation of the anti-apoptotic factor B-cell lymphoma-extra large (Bcl-xL). This study aimed to determine whether myofibroblasts become steroid-resistant via Bcl-xL expression in vivo and in vitro. A steroid-resistant asthma model was developed by repeatedly challenging sensitized BALB/c mice intratracheally with a high dose of ovalbumin (OVA). Myofibroblasts were identified by flow cytometry as α-smooth muscle actin (α-SMA) CD31 CD45 CD326 cells. Lung mesenchymal stem cells (MSCs; platelet-derived growth factor receptor α CD31 CD45 CD326 cells) were isolated and differentiated into myofibroblasts by culturing them with 15% fetal bovine serum (FBS) for 6 d. In asthmatic lungs, α-SMA myofibroblasts showed increased Bcl-xL expression, which was unaffected by dexamethasone (DEX) treatment. However, co-treatment with the Bcl-xL inhibitor navitoclax significantly restored steroid sensitivity. In vitro, MSCs were susceptible to DEX-induced early apoptosis, whereas differentiated myofibroblasts were resistant to DEX-induced apoptosis and strongly expressed Bcl-xL. In other words, navitoclax treatment overcame steroid resistance in cultured myofibroblasts. These findings indicate that Bcl-xL-expressing myofibroblasts contribute to the development of glucocorticoid resistance in fibrotic lungs in severe asthma. Targeting Bcl-xL may provide a novel therapeutic strategy to restore steroid responsiveness in severe asthma. - Source: PubMed
Matsuda MasayaShimora HayatoMaeyama HirotoTakatani YumaNagatani YukinoMakishima MomokaSannomiya YuyaKaibori YuichiroYamagishi NobuyukiKaminuma OsamuNabe Takeshi - Cyclin-dependent kinases (CDKs) play a crucial role in cell cycle (such as CDK1 and CDK4/6) and transcription (such as CDK7, CDK9, and CDK12/13). While CDK inhibitors are clinically effective in cancer therapy, their mechanisms of apoptosis induction remain incompletely understood. Here, we demonstrate that inhibition of CDKs involved in cell cycle control (such as CDK1 or CDK4/6) displays no cytotoxic potential. Surprisingly, inhibition of CDK7, which is involved in the control of cell cycle and transcriptional initiation, also showed no cytotoxicity. Only inhibition of CDK9 (by AZD4573 and atuveciclib) or of CDK12/13 (by SR4835 and THZ531)-which target the transcriptional elongation of RNA polymerase II (RNAPII)-exerted a strong apoptotic potential. Since CDK9 and CDK12/13 target different elongation factors associated with RNAPII (such as SPT6 and NELF for CDK9; CDC73, and LEO1 for CDK12/13), they cannot substitute for each other. Consequently, the combination of AZD4573 with SR4835 resulted in significant, synergistic cytotoxicity. Inhibiting CDK9 or CDK12/13 induced the rapid downregulation of the short-lived, anti-apoptotic Bcl-2 proteins Mcl1 and A1/Bfl1 in Jurkat leukemia cells and SUDHL1 lymphoma cells, whereas the expression of Bcl-2 and Bcl-xL remained unaffected. Since Mcl1 and A1 antagonize the pro-apoptotic Bcl-2 proteins Bak and Bax, apoptosis induction by AZD4573 or SR4835 was blocked in Bak- and Bax/Bak-deficient Jurkat cells and strongly reduced in Bax-deficient cells. Because Bcl-2 only inhibits Bax, but not Bak, AZD4573 and SR4835 were able to induce apoptosis in Jurkat cells overexpressing Bcl-2. As tumor cells frequently upregulate Bcl-2, inhibitors of CDK9 and CDK12/13 represent promising anticancer drugs. - Source: PubMed
Publication date: 2026/05/27
Krings Karina SHatzfeld JudithWeller SandraBorkowski NadineLlewellyn Tanya RSchmitt LauraScherer BoItkonen Harri MPeter ChristophStork BjörnGeyh StefanieEickhoff JanKlebl BertQin NanEssmann FrankWesselborg Sebastian - : Excessive dietary inorganic phosphate (Pi) as a food additive poses potential health risks. : This study investigated the impact of excessive dietary inorganic phosphate on intestinal and immune homeostasis in mice using gradient Pi exposure combined with an inflammatory model. : Pi overload induced atrophy in the thymus, spleen, and kidney; damaged the intestinal barrier; reduced the villus height-to-crypt-depth ratio; and decreased goblet cell numbers. Altered levels of serum sIgA and IgE, as well as intestinal IgA, IgG, IgE, and IgM, together with decreased IFN-α, indicated altered levels of immunoglobulins and cytokines under Pi treatment. Proteomic analysis revealed differential expression of key proteins, including CNTFR and Bcl2l1 in the JAK/STAT pathway and metabolic regulators CPT1α and IDH1, when comparing Pi-treated mice with the control group. : These preliminary findings suggest that Pi may affect intestinal mucosal barrier function and systemic immune response through immune regulation and mitochondrial metabolic pathways, providing preliminary insight into the potential health implications of Pi overconsumption in humans. - Source: PubMed
Publication date: 2026/05/16
Sun ZongchaoHuang ShiyaZhao YuxinLuan YunhanWang YinuoWang RunzheWu WeiweiHuang DanliLiu JiankangZhang Yinghui - Proteolysis-targeting chimeras (PROTACs) offer a promising approach to degrade traditionally "undruggable" proteins, surpassing limitations of conventional inhibitors. However, current small-molecule PROTACs suffer from poor membrane permeability attributed to large molecular size, along with undesirable off-target toxicity. In this study, leveraging a novel pretargeted strategy, we developed a peptide-based delivery platform to overcome these limitations. Using the PROTAC DT2216 as a model, this pretargeted system integrates the self-assembling peptide TPE-GK-N (targeting tumor integrin αβ RGD and forming surface-adherent nanofibers) and the DT2216-loaded liposome DSPE-PEG-DBCO. The N-DBCO bioorthogonal pair was designed to facilitate membrane-localized recruitment of DBCO-functionalized liposomes by the azide-bearing peptide, thereby improving tumor-targeted delivery. , the system (TPE-GK-N+DSPE-PEG-DBCO@DT2216) showed significantly enhanced target protein Bcl-xL degradation, cytotoxicity, apoptosis induction, and inhibition of cell migration in MDA-MB-231 cells compared to the free DT2216. , the system demonstrated profound tumor growth suppression (about 65% inhibition) with no obvious toxicity to normal tissues. This study demonstrates a pretargeted peptide strategy for PROTAC delivery, significantly enhancing anticancer efficacy while mitigating systemic toxicity, offering a promising strategy for future PROTAC development. - Source: PubMed
Publication date: 2026/05/25
Wu QianqianZhang ChenLi YuanhengZhang MiaoYan HaoXu NaihanTan ChunyanTan Ying - The HBx protein from Hepatitis B virus (HBV) is essential for replication and promotes pathogenicity during chronic infection. HBx hijacks host proteins, reprogramming them to evade antiviral defence. However, the structural basis of recruitment remains largely unknown. The HBx isoform derives from integration of viral DNA into the host genome and is linked to hepatocellular carcinoma. We present an NMR-based setup to characterize HBx-host protein interactions at residue-level resolution. HBx is disordered in isolation but undergoes local folding upon binding apoptosis regulator Bcl-xL and epigenetic reader Spindlin1. The HBx-Spindlin1 complex is bivalent: a hydrophobic interaction combines with a sticky patch realized via a rare inter-molecular zinc finger. HBx thus conceals the region responsible for recruiting Spindlin1 to histone tails, promoting transcription of extrachromosomal viral DNA. This mechanism exemplifies the capacity of HBx to engage diverse host factors into dynamic complexes. - Source: PubMed
Publication date: 2026/05/25
Clavier AlexisShida ToshinobuDroemer Maxim AGómez-Evain Santiagovon Hammerstein FranziskaHolzinger JulianLeuthold Mila MDouat CélineSchütz Anne K