ASNA1 Blocking Peptide, Blocking Peptides
- Known as:
- ASNA1 Blocking Peptide, Blocking Peptides
- Catalog number:
- 33R-2281
- Product Quantity:
- 100 ug
- Category:
- -
- Supplier:
- Fitzgerald
- Gene target:
- ASNA1 Blocking Peptide Peptides
Related genes to: ASNA1 Blocking Peptide, Blocking Peptides
- Gene:
- ASNA1 NIH gene
- Name:
- arsA arsenite transporter, ATP-binding, homolog 1 (bacterial)
- Previous symbol:
- -
- Synonyms:
- ARSA-I, GET3, TRC40
- Chromosome:
- 19p13.13
- Locus Type:
- gene with protein product
- Date approved:
- 1997-07-01
- Date modifiied:
- 2019-04-12
Related products to: ASNA1 Blocking Peptide, Blocking Peptides
Related articles to: ASNA1 Blocking Peptide, Blocking Peptides
- The BCL2-like protein MCL1 plays pivotal roles in apoptosis and non-apoptotic functions. While many BCL2 family members are predicted to be tail-anchored (TA) proteins, direct evidence for MCL1's membrane targeting via the GET pathway, a major pathway for membrane insertion of TA proteins, has been lacking. Using degron-mediated depletion of GET3 (ASNA1/TRC40) in human cell lines, we uncovered a role of GET3 in regulating apoptosis. Depleting GET3 induced a slowdown of the cell cycle in HeLa and non-cancerous RPE1 cells. However, GET3 deficiency induced a more pronounced toxicity in HeLa cells, marked by enhanced apoptosis and reduced clonogenic survival. Notably, MCL1 expression diminished upon GET3 depletion and increased with GET3 overexpression, suggesting that MCL1 may be a TA-containing cargo of GET3. Moreover, we observed a direct interaction between GET3 and MCL1 via the C-terminal hydrophobic tail. Functionally, GET3 depletion enhanced apoptosis triggered by pharmaceutical inhibition of MCL1. Furthermore, GET3 deficiency promoted MCL1 downregulation and accelerated apoptosis during prolonged mitotic arrest. These findings underscore the importance of the GET pathway in regulating apoptosis and MCL1's tail-anchoring. - Source: PubMed
Publication date: 2026/05/07
Yu Chun YinDu MingxuanYeung Tsz KwanPoon Randy Yat Choi - PROteolysis TArgeting Chimeras are attracting growing interest in pharmaceutical research thanks to their catalytic and irreversible mechanism, which is capable of targeting proteins previously considered "undruggable". These bifunctional molecules hijack the cellular ubiquitin-proteasome system by recruiting E3 ligases (such as CRBN or VHL) to induce the selective degradation of a target protein. Their efficacy has been demonstrated against various disorders and several compounds have reached phase I-III clinical trials, reinforcing their appeal. In the fight against toxins, derivatives of the Retro-2 molecule (active against Shigatoxins, ricin, and various pathogens) have been developed. These molecules act on host cells by disrupting the intracellular trafficking of pathogens, targeting in particular the Sec16A and/or ASNA1 proteins. Our study presents the synthesis and characterization of new chemical probes based on PROTAC technology, combining a CRBN ligand derived from thalidomide, a Retro-2 derivative, and variable-length PEG chain linkers to better understand the mechanism of action of Retro-2-derived molecules. Contrary to initial assumptions, our results do not show proteasome-dependent degradation of the protein targets, but demonstrate that PEG-2 molecules can degrade the translation termination factor GSPT1 despite the normally propitious anchoring of the PEG linker at position 4 of the phthalimide ring. Furthermore, this study shows for the first time that GSPT1 degradation depends on the length of the flexible PEG chain linker. - Source: PubMed
Publication date: 2026/02/05
Michon MarineCurpanen SebastienPessey OmbelineThai RobertGaillard Jean-CharlesHerbette GaëtanHinsinger KarenGillet DanielArmengaud JeanCintrat Jean-ChristopheBarbier Julien - Recent studies have linked compound heterozygous mutations in ASNA1 to progressive dilated cardiomyopathy and early infantile mortality in humans. However, the specific role of ASNA1 in cardiomyocytes and the molecular mechanisms underlying ASNA1-related cardiomyopathy remain poorly understood. Tail-anchored (TA) proteins, characterized by a single C-terminal transmembrane domain (TMD), require post-translational targeting to intracellular membranes, a process primarily mediated by the evolutionarily conserved Guided Entry of Tail-anchored proteins (GET) pathway in yeast and the Transmembrane Recognition Complex (TRC) pathway in mammals. ASNA1 (also known as TRC40 or GET3) serves as the central ATP-dependent chaperone delivering TA proteins to the endoplasmic reticulum (ER) membrane. To address ASNA1's role in the heart, we generated constitutive and inducible cardiomyocyte-specific Asna1 knockout mouse models. Constitutive Asna1 deletion during embryogenesis caused perinatal lethality with marked ventricular myocardial thinning by embryonic day 16.5, whereas inducible deletion in adult cardiomyocytes led to rapid ventricular dilation, impaired cardiac function, pathological remodeling, and early mortality. Mechanistically, ASNA1 deficiency destabilized the pre-targeting complex and reduced the expression of multiple TA protein substrates, impairing membrane trafficking and protein transport. Transcriptomic analyses revealed compensatory upregulation of genes involved in protein trafficking and Golgi-to-ER transport, reflecting maladaptive responses to disrupted vesicular transport. Collectively, our findings identify ASNA1 as a critical regulator of TA protein stability and vesicular trafficking in cardiomyocytes, whose loss disrupts cardiac proteostasis and contributes to the cardiomyopathy pathogenesis. Our work provides mechanistic insights into ASNA1-related cardiac disease and highlights potential therapeutic targets. - Source: PubMed
Publication date: 2025/12/10
Feng WeiZhang ZengmingChen ZeyuWang LiYe MaoGu YusuHuang TitaniaNgo HarrisonChen Ju - : Prepulse inhibition (PPI) is a robust, reproducible phenotype associated with schizophrenia and other psychiatric disorders. This study was carried out to identify gene(s) influencing PPI. : We performed Quantitative Trait Locus (QTL) analysis of PPI in 59 strains from the BXD recombinant inbred (BXD RI) mouse family and used a 2-LOD region for candidate gene identification. Genes significantly correlated with the candidate gene were identified based on genetic, partial, and literature correlation, and were further studied through gene enrichment and protein-protein interaction analyses. Phenome-wide association study (PheWAS) and differential expression analyses of the candidate gene were performed using human data. : We identified one significant (GN Trait 11428) and two suggestive male-specific QTLs (GN Traits 11426 and 11427) on Chromosome 19 between 27 and 36 Mb with peak LRS values of 19.2 (-logP = 4.2), 14.4 (-logP = 3.1), and 13.3 (-logP = 2.9), respectively. , ATPase family, AAA domain containing 1 was identified as the strongest candidate for the male-specific PPI loci. expression in BXDs is strongly -modulated in the nucleus accumbens (NAc, LRS = 26.5 (-logP = 5.7). Many of the -correlated genes in the NAc were enriched in neurotransmission-related categories. Protein-protein interaction analysis suggested that ATAD1 functions through its direct partners, GRIA2 and ASNA1. PheWAS revealed significant associations between and psychiatric traits, including schizophrenia. Analysis of a human RNA-seq dataset revealed differential expression of between schizophrenia patients and the control group. : Collectively, our analyses support as a potential candidate gene for PPI and suggest that this gene should be further investigated for its involvement in psychiatric disorders. - Source: PubMed
Publication date: 2025/09/26
Bajpai Akhilesh KFreels Timothy GLu LuCook Melloni N - The monocyte adhesion to vascular endothelial cells constitutes a key step in atherosclerosis pathogenesis. We previously found that ROS-autophagy pathway participated in the monocyte-endothelial cell adhesion induced by angiotensin domain type 1 receptor-associated proteins (APJ) and its endogenous ligand apelin-13. In this study, we investigated what specific type of autophagy apelin-13 regulated in this process. By conducting full-scale transcriptomic analysis in apelin-13-treated human umbilical vein endothelial cells (HUVECs), we found that the transcription levels of ER-phagy receptor protein SEC62 were significantly elevated. Importantly, SEC62 was also upregulated in human atherosclerotic lesions. Thus, we investigated the effects of SEC62-dependent ER-phagy on apelin-13-induced monocyte-endothelial cell adhesion and atherosclerosis pathogenesis. We demonstrated that Apelin-13 (0.001-1 μM) dose-dependently upregulated SEC62 expression thereby inducing ER-phagy in HUVECs. This effect was reversed by autophagy inhibitor 3MA (10 mM) and endoplasmic reticulum stress inhibitor salubrinal (10 μM). The siRNA-Sec62, 3MA (10 mM), and salubrinal (10 μM) all inhibited apelin-13-induced monocyte-endothelial cells adhesion, whereas vascular endothelial cells specific SEC62 deletion alleviated atherosclerotic plaques area, intercellular adhesion molecules expression and lesional macrophages in apelin-13-treated APOE mice with high-fat and high-cholesterol diet. Moreover, we demonstrated that ubiquitin-like modification of ALDH1L1 was involved in SEC62-dependent ER-phagy in apelin-13-treated HUVECs: apelin-13 upregulated small ubiquitin-like protein UBL4A, which mediated the ubiquitination-like modification of ALDH1L1 at 812-lysine site. This, in turn, promoted insertion of ALDH1L1 into ER membrane and led to SEC62-dependent ER-phagy. We showed that siRNA-UBL4A, siRNA-ALDH1L1, siRNA-ASNA1, and the mutant of 812 lysine site of ALDH1L1 all decreased apelin-13-induced monocyte-endothelial cell adhesion. We conclude that apelin-13 induces SEC62-dependent ER-phagy to promote monocyte-endothelial cell adhesion and atherosclerosis. This study reveals new mechanisms underlying atherosclerosis and identifies a potential therapeutic target. - Source: PubMed
Publication date: 2025/02/10
Chen ZheCheng JunZhou QunWu Le-leChen Jia-WeiDuan Xiang-NingYan Jia-LongCao Jian-GangXia Xiao-DanLi Lan-FangChen Lin-Xi