Mouse polyclonal to KLHDC3, Host Mouse
- Known as:
- Mouse pab KLHDC3, Host Mouse
- Catalog number:
- YF-PA26830
- Product Quantity:
- 50 uL
- Category:
- -
- Supplier:
- Abfron
- Gene target:
- Mouse polyclonal KLHDC3 Host
Related genes to: Mouse polyclonal to KLHDC3, Host Mouse
- Gene:
- KLHDC3 NIH gene
- Name:
- kelch domain containing 3
- Previous symbol:
- -
- Synonyms:
- PEAS, hPeas, dJ20C7.3
- Chromosome:
- 6p21.1
- Locus Type:
- gene with protein product
- Date approved:
- 2003-06-02
- Date modifiied:
- 2014-11-19
Related products to: Mouse polyclonal to KLHDC3, Host Mouse
Related articles to: Mouse polyclonal to KLHDC3, Host Mouse
- RECQL4, a RecQ family helicase, is essential for DNA replication and genome stability. Mutations in RECQL4 cause severe human disorders yet we do not fully understand its functions, particularly regarding ATP-dependent helicase activity. To understand RECQL4's functions further, we performed a genome-wide forward genetic screen using a murine model harbouring patient-like RECQL4 mutations. We identify KLHDC3, a substrate-binding subunit of the Cullin-RING ligase E3 complex, loss as the most significant rescue allele. KLHDC3 loss restores proliferation and replication in RECQL4-deficient cells by stabilizing trace levels of a truncated RECQL4 fragment containing the N-terminal 480 amino acids, lacking the helicase and C-terminal regions. This RECQL4 fragment forms after Cre-mediated recombination of the Recql4 allele and contains a neo-degron sequence specific for KLHDC3. Although this mechanism does not apply to human mutations, it demonstrates that minimal RECQL4 levels, without any ATPase domain/activity, are sufficient to support DNA replication. This demonstrates that RECQL4 is an essential and non-redundant regulator of DNA replication and cell viability and that this activity does not require its ATP-dependent helicase activity. - Source: PubMed
Publication date: 2026/03/10
Buco Paula Armina VCastillo-Tandazo WilsonChalk Alistair MPilcher CourtneyHolien Jessica KHeierhorst JörgTan Tiong YKoren AmnonSmeets Monique FWalkley Carl R - : The exact pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder, remains unclear. Ferroptosis is a form of cell death characterized by intracellular iron accumulation, and has emerged as a potential contributor to the pathological cascade of AD. Therefore, this study aims to identify core genes that may function as reliable biomarkers for AD through an in-depth analysis of the genetic relationship between ferroptosis-related genes and AD. : This study first obtained the gene expression profiles (GSE140831, GSE63060 and GSE63061 expression profiles). The GSE140831 dataset served as the discovery cohort, and the GSE63060 and GSE63061 datasets were used as independent validation cohorts. R language 4.4.1 was used for standardizing and identifying differentially expressed genes (DEGs) in AD patients in all datasets. Secondly, the ferroptosis-related genes were obtained. By integrating the ferroptosis-related genes, ferroptosis-related DEGs (FRDEGs) were detected. Then, the FRDEGs were verified and evaluated, and the biological functions of the core genes were analyzed. Finally, miRNAs interacting with these core FRDEGs were explored. : The study identified nine FRDEGs (ACVR1B, BRPF1, G6PD, KLHDC3, LAMP2, MTCH1, P4HB, PTPN6, RBMS1), which are potentially related and may serve as biomarkers for AD. All nine genes demonstrated statistically significant differential expression (up-regulation) in both independent validation cohorts and in the combined analysis ( < 0.05). Although the area under the curve (AUC) values of these nine genes ranged from 0.61 to 0.71, indicating moderate discriminatory power, these findings suggest that they may be involved in pathways related to AD and are worthy of further investigation as potential auxiliary biomarkers. Finally, a network of hub FRDEGs-miRNAs interaction was constructed. There were 11 miRNAs that may regulate these hub FRDEGs simultaneously. : This study showed the significant association of the identified FRDEGs with AD. Also, a core ferroptosis-related biomarker network for miRNAs regulation of AD was constructed. The specific regulatory mechanism is worthy of further investigation. - Source: PubMed
Publication date: 2026/02/11
Liu WenjiaRao XinYu Liyang - BACKGROUND: Protein ubiquitination is a key post-translational modification that governs protein stability and cellular homeostasis. KLHDC3 is a substrate recognition receptor in the recently identified C-terminal degron-mediated DesCEND ubiquitination pathway. It selectively binds proteins with C-terminal RxxxG motifs, targeting them for degradation. While N-terminal degron pathways are well-characterized, the physiological roles of C-terminal degrons remain poorly understood. To explore KLHDC3’s function in a physiological context, we generated mice deficient in the Klhdc3 gene. RESULTS: Klhdc3-deficient mice exhibited sub-Mendelian birth rates and progressive postnatal lethality, with a median survival of 136 days and a maximum lifespan of approximately one year. Surviving mice showed early growth retardation followed by normalization of body mass, and later developed pronounced obesity, with some individuals reaching fat mass levels exceeding 50% of total body weight. Transcriptomic and proteomic analyses of Klhdc3−/− embryonic fibroblasts revealed significant changes in protein expression with minimal alterations in transcript levels, consistent with KLHDC3’s role in post-translational regulation. Among the upregulated proteins, HINT1 was identified as a novel KLHDC3 substrate containing a C-terminal degron motif. Protein stability assays and immunoblotting confirmed HINT1 as a candidate target of KLHDC3. CONCLUSIONS: This study establishes a physiological role for the DesCEND pathway in vivo and identifies KLHDC3 as a critical regulator of development, survival, and adiposity in mice. The identification of HINT1 as a putative KLHDC3 substrate expands our understanding of C-terminal degron-mediated protein regulation and suggests broader implications for developmental and metabolic processes. - Source: PubMed
Publication date: 2026/01/28
Buco Paula Armina VHoque AshfaqulCastillo-Tandazo WilsonChalk Alistair MSmeets Monique FWalkley Carl R - Targeted protein degradation modulates protein function beyond the inhibition of enzyme activity or protein-protein interactions. Most degrader drugs function by directly mediating the proximity between a neosubstrate and a hijacked E3 ligase. Here we identify pseudo-natural products derived from (-)-myrtanol, termed iDegs, that inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDegs boost IDO1 ubiquitination and degradation by the cullin-RING E3 ligase CRL2, which we identified to natively mediate ubiquitin-mediated degradation of IDO1. Therefore, iDegs increase IDO1 turnover using the native proteolytic pathway. In contrast to clinically explored IDO1 inhibitors, iDegs reduce the formation of kynurenine by both inhibition and induced degradation of the enzyme and thus also modulate the non-enzymatic functions of IDO1. This unique mechanism of action may open up alternative therapeutic opportunities for the treatment of cancer beyond classical inhibition of IDO1. - Source: PubMed
Publication date: 2026/01/07
Hennes ElisabethLucas BelénScholes Natalie SCheng Xiu-FenScott Daniel CBischoff MatthiasReich KatharinaGasper RaphaelLucas MaríaXu Teng TengRossini SofiaPulvermacher Lisa-MarieDötsch LaraImrichova HanaBrause AlexandraFührer SiskaNaredla Kesava ReddySievers SonjaKumar KamalJanning PetraOrabona CirianaGersch MalteMurray Peter JSchulman Brenda AWinter Georg EZiegler SlavaWaldmann Herbert - RECQL4 is a member of the RecQ family of helicases, playing essential roles in DNA replication and maintaining genome integrity. Mutations in RECQL4 are linked to severe human diseases, including Rothmund-Thomson Syndrome, RAPIDALINO Syndrome, and Baller-Gerold Syndrome. However, we still do not fully understand its functions and genetic interactions. The role of the ATP-dependent helicase activity in RECQL4 remains controversial. To understand RECQL4's functions further, we conducted a genome-wide forward genetic screen using murine models that closely mimic the RECQL4 mutations found in patients with Rothmund-Thomson syndrome. Our goal was to identify loss-of-function alleles that could rescue the proliferation and viability defects associated with RECQL4 mutation. From our screening we identified the loss of KLHDC3, a substrate-binding subunit of the Cullin-RING ligase (CRL) E3, as the most significant rescue allele. KLHDC3 facilitates the ubiquitin-mediated destruction of proteins with specific C-terminal degron motifs. Its loss normalized cell proliferation and DNA replication rates in cells with mutated RECQL4. Further analysis revealed that the loss of KLHDC3 led to the stabilization of minute levels of a truncated RECQL4 protein. This RECQL4 fragment contained a neo-degron sequence specific for KLHDC3, formed after Cre-mediated recombination of the allele. Although this rescue mechanism does not apply to human RECQL4 mutations, it shows that very low chromatin-bound levels of a truncated RECQL4 protein-comprising only the N-terminal 480 amino acids, including its Sld2-like domain but lacking the ATP-dependent helicase domain and the entire C-terminal portion-are sufficient to support DNA replication in mammalian cells. These results demonstrate that the ATPase activity and helicase domain of RECQL4 are not essential for DNA replication in mammals. Furthermore, our findings suggest that there are unlikely to be monogenic loss-of-function alleles that can rescue RECQL4 mutations. This demonstrates that RECQL4 is an essential and non-redundant regulator of DNA replication and cell viability and that this activity does not require the ATP dependent helicase activity. - Source: PubMed
Publication date: 2025/07/21
Buco Paula Armina VTandazo-Castillo WilsonChalk Alistair MPilcher CourtneyHolien Jessica KHeierhorst JörgTan Tiong YKoren AmnonSmeets Monique FWalkley Carl R