KLHDC5 Blocking Peptide
- Known as:
- KLHDC5 Blocking Peptide
- Catalog number:
- 33r-5301
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Fitzgerald industries international
- Gene target:
- KLHDC5 Blocking Peptide
Related genes to: KLHDC5 Blocking Peptide
- Gene:
- KLHL42 NIH gene
- Name:
- kelch like family member 42
- Previous symbol:
- KLHDC5
- Synonyms:
- KIAA1340, Ctb9
- Chromosome:
- 12p11.22
- Locus Type:
- gene with protein product
- Date approved:
- 2005-02-08
- Date modifiied:
- 2015-11-18
Related products to: KLHDC5 Blocking Peptide
Related articles to: KLHDC5 Blocking Peptide
- Age is the strongest risk factor for type 2 diabetes, yet their independent contribution to pancreatic islet dysfunction remains unclear. We integrate DNA methylation, transcriptomic, and genotyping data from 144 islet donors. We identify 996 age- and 902 T2D-associated CpGs with minimal overlap, and 251 age- and 310 diabetes CpG target genes, usually distant from the CpG. Age-linked CpGs are enriched in promoters, form co-regulated gene modules, link to beta-cell function, including insulin secretion. Diabetes-associated CpGs are enriched in enhancer/non-regulatory regions, and modules suggest stress-induced epigenetic drift. CpG-gene associations are independent of genetic variation. Mendelian randomisation supports a causal role for age-associated CpGs regulating KLHL42, a T2D GWAS locus. A blood-based methylation risk score based on age-linked CpGs correlates with insulin secretion and improves diabetes classification when combined with genetic risk (AUC = 0.91). Altogether, age is associated with a coordinated epigenetic programme, whereas diabetes links to a heterogeneous, stress-related epigenetic signature. - Source: PubMed
Publication date: 2026/06/03
Maurin LucasMarselli LorellaBoissel MathildePascat VincentSuleiman MaraHenriques EmmaDe Luca CarmelaNing LijiaoFourcot MarieTesi MartaToussaint BénédicteAmanzougarene SouhilaDerhourhi MehdiOger FrédérikBurdet FredericCanouil MickaelCnop MiriamIbberson MarkBonnefond AmélieMarchetti PieroFroguel PhilippeKhamis Amna - Systemic characterization of genes and pathways underlying the genetic architecture of type 2 diabetes (T2D) requires scalable functional genomics approaches. Molecular readouts from CRISPR perturbations can effectively uncover the mechanistic effects of underexplored genes. Here we performed single-cell RNA sequencing on pooled CRISPR screens (Perturb-seq) of 61 T2D-associated genes and 40 ribosome-associated quality control (RQC) genes in human pancreatic β cells (EndoC-βH1) for investigations of insulin production and T2D pathology. We identified 21 functional genes, including the uncharacterized KLHL42 and ZZEF1. Findings from global and β cell-specific knockout male mice, islet organoids and human islets reveal that ZZEF1 is a regulator of insulin synthesis and β cell stress through ribosomal stress-surveillance pathways in working and stress status-defined β cell subtypes. ZZEF1 deficiency impairs β cell function by inhibiting the RQC sensor EDF1, which could be improved by azoramide and ISRIB treatments. These Perturb-seq analyses and identification of functional RQC-related genes can provide potential therapeutic targets for T2D. - Source: PubMed
Publication date: 2026/01/02
Nan JingminjieHe XianglongLiu XiaopingRan JianrongChen JiahuanLi PengxiaoLiu DongxueSun YananShan AijingJiang XiuliXie JingWang WeiqingNing GuangCao Yanan - CDK4/6 inhibitors (CDK4/6i) show anticancer activity in certain human malignancies, such as breast cancer. However, their application to other tumor types and intrinsic resistance mechanisms are still unclear. Here, we demonstrate that MYC amplification confers resistance to CDK4/6i in bladder, prostate and breast cancer cells. Mechanistically, MYC binds to the promoter of the E3 ubiquitin ligase KLHL42 and enhances its transcription, leading to RB1 deficiency by inducing both phosphorylated and total pRB1 ubiquitination and degradation. We identify a compound that degrades MYC, A80.2HCl, which induces MYC degradation at nanomolar concentrations, restores pRB1 protein levels and re-establish sensitivity of MYC high-expressing cancer cells to CDK4/6i. The combination of CDK4/6i and A80.2HCl result in marked regression in tumor growth in vivo. Altogether, these results reveal the molecular mechanisms underlying MYC-induced resistance to CDK4/6i and suggest the utilization of the MYC degrading molecule A80.2HCl to potentiate the therapeutic efficacy of CDK4/6i. - Source: PubMed
Publication date: 2024/02/29
Ma JianLi LeiMa BohanLiu TianjieWang ZixiYe QiPeng YunhuaWang BinChen YuleXu ShanWang KeDang FabinWang XinyangZeng ZixuanJian YanlinRen ZhihuaFan YizengLi XudongLiu JingGao YangWei WenyiLi Lei - Renal tubulointerstitial fibrosis (TIF) is considered as the final convergent pathway of diabetic nephropathy (DN) without effective therapies currently. MiRNAs play a key role in fibrotic diseases and become promising therapeutic targets for kidney diseases, while miRNA clusters, formed by the cluster arrangement of miRNAs on chromosomes, can regulate diverse biological functions alone or synergistically. In this study, we developed clustered miR-23a/27a/26a-loaded skeletal muscle satellite cells-derived exosomes (Exos) engineered with RVG peptide, and investigated their therapeutic efficacy in a murine model of DN. Firstly, we showed that miR-23a-3p, miR-26a-5p and miR-27a-3p were markedly decreased in serum samples of DN patients using miRNA sequencing. Meanwhile, we confirmed that miR-23a-3p, miR-26a-5p and miR-27a-3p were primarily located in proximal renal tubules and highly negatively correlated with TIF in db/db mice at 20 weeks of age. We then engineered RVG-miR-23a/27a/26a cluster loaded Exos derived from muscle satellite cells, which not only enhanced the stability of miR-23a/27a/26a cluster, but also efficiently delivered more miR-23a/27a/26a cluster homing to the injured kidney. More importantly, administration of RVG-miR-23a/27a/26a-Exos (100 μg, i.v., once a week for 8 weeks) significantly ameliorated tubular injury and TIF in db/db mice at 20 weeks of age. We revealed that miR-23a/27a/26a-Exos enhanced antifibrotic effects by repressing miRNA cluster-targeting Lpp simultaneously, as well as miR-27a-3p-targeting Zbtb20 and miR-26a-5p-targeting Klhl42, respectively. Knockdown of Lpp by injection of AAV-Lpp-RNAi effectively ameliorated the progression of TIF in DN mice. Taken together, we established a novel kidney-targeting Exo-based delivery system by manipulating the miRNA-23a/27a/26a cluster to ameliorate TIF in DN, thus providing a promising therapeutic strategy for DN. - Source: PubMed
Publication date: 2023/08/18
Ji Jia-LingShi Hui-MinLi Zuo-LinJin RanQu Gao-TingZheng HuiWang EQiao Yun-YangLi Xing-YueDing LingDing Da-FaDing Liu-ChengGan Wei-HuaWang BinZhang Ai-Qing - Sézary syndrome (SS) is a rare and aggressive type of cutaneous T cell lymphoma (CTCL) with a poor prognosis. Intra-tumoral heterogeneity caused by different disease compartments (e.g., skin, blood) and poor understanding of the pathogenesis has created obstacles to the precise diagnosis and targeted treatment of the disease. Here we performed a comprehensive analysis by integrating single-cell transcriptomic data of 40,333 peripheral blood mononuclear cells (PBMCs) and 41,580 skin cells, as well as single-cell chromatin accessibility data of 11,058 PBMCs from an SS patient and matched healthy controls (HCs). Validation and functional investigation were carried out in an independent cohort consisting of SS patients, mycosis fungoides (MF) patients, psoriatic erythroderma patients, and HCs, as well as multiple cell lines. The analysis revealed that skin-derived Sézary cells (SCs) had a shifting trend to more advanced mature phenotypes compared to blood-derived SCs. A series of specific marker genes (TOX, DNM3, KLHL42, PGM2L1, and SESN3) shared in blood- and skin-derived SCs were identified, facilitating the diagnosis and prognosis of MF/SS. Moreover, luciferase reporter assays and gene knockdown assays were used to verify that KLHL42 was transcriptionally activated by GATA3 in SS. Functional assays indicated that KLHL42 silencing significantly inhibited aggressive CTCL cell proliferation and promoted its apoptosis. Therefore, targeting inhibition KLHL42 might serve as a promising therapeutic approach in CTCL. - Source: PubMed
Publication date: 2022/11/18
Xue XiaotongWang ZhenzhenMi ZihaoLiu TingtingWang ChuanShi PeidianSun LeleYang YongliangLi WenchaoWang ZheLiu HongZhang Furen