Ask about this productRelated genes to: AP3S1 Blocking Peptide
- Gene:
- AP3S1 NIH gene
- Name:
- adaptor related protein complex 3 subunit sigma 1
- Previous symbol:
- CLAPS3
- Synonyms:
- -
- Chromosome:
- 5q22.3-q23.1
- Locus Type:
- gene with protein product
- Date approved:
- 1996-03-12
- Date modifiied:
- 2018-06-22
Related products to: AP3S1 Blocking Peptide
Related articles to: AP3S1 Blocking Peptide
- Autophagy-mitophagy pathways are essential for regulating immune homeostasis. However, their contribution to population-level chronic low-grade systemic inflammation (SI) remains unclear. The objective was to investigate the association between variation in the genes related to the autophagy-mitophagy pathways and SI, and to examine whether lifestyle factors modify this relationship. We conducted genome-wide association studies and gene-set enrichment analyses using data from the Korean Genome and Epidemiology Study (KoGES, n = 28,102) and UK Biobank (UKBB, n = 343,892). SI was defined as an elevated white blood cell count or high-sensitivity C-reactive protein. Using Core Longevity State Vectors (CLSVs)-gene sets representing immune-longevity pathways derived from comparative transcriptomic analysis-we tested six pathways and constructed a weighted genetic risk score (GRS) from significant variants. Gene-lifestyle interactions were examined with respect to major dietary and lifestyle factors. Among six CLSVs, only CLSV-2 (mitophagy and autophagy) showed a significant association with SI (β = 0.425, = 0.008). Six single nucleotide polymorphisms (SNPs) in autophagy-mitophagy genes (, , , , , and ) were associated with SI in KoGES ( < 5 × 10), and ten SNPs (genes selected in KoGES plus , , , ) reached genome-wide significance in UKBB ( < 5 × 10). A higher GRS was associated with increased SI in both cohorts and was strongly associated with metabolic syndrome (MetS, OR = 1.91 in KoGES; OR = 1.62 in UKBB). SI was characterized by neutrophilia with relative lymphopenia. In UKBB, significant gene-lifestyle interactions were observed for diet, physical activity, smoking, and alcohol ( < 0.01). Favorable lifestyle factors reduced SI most effectively in individuals with protective genotypes. Among individuals with a high vegetable/fruit intake, SI prevalence was 35%, 36%, and 38% in the negative-, zero-, and positive-GRS groups, respectively, compared with 36%, 45%, and 48% in the low-intake groups. In conclusion, genetic variations in autophagy-mitophagy pathways specifically influence SI. Genetic predisposition substantially modifies the benefits of lifestyle, underscoring the importance of integrating genetic and lifestyle factors in understanding SI susceptibility. - Source: PubMed
Publication date: 2026/03/27
Choi YoungjinPark Sunmin - Mechanisms of tumorigenesis in sinonasal squamous cell carcinoma (SNSCC) remain poorly understood due to its rarity. A subset of SNSCC is associated with human papillomavirus (HPV), but it is unclear whether HPV drives tumorigenesis or acts as a neutral bystander. Here, we show that HPV-associated SNSCC shares mutational patterns found in HPV-associated cervical and head and neck squamous cell carcinoma, including lack of TP53 mutations, hotspot mutations in PI3K and FGFR3, enrichment of APOBEC mutagenesis, viral integration at known hotspots, and frequent epigenetic regulator alterations. We identify HPV-associated SNSCC-specific recurrent mutations in KMT2C, UBXN11, AP3S1, MT-ND4, and MT-ND5, with KMT2D and FGFR3 mutations correlating with reduced overall survival. We establish an HPV-associated SNSCC cell line, showing that combinatorial small-molecule inhibition of YAP/TAZ and PI3K synergistically suppresses clonogenicity. Combining YAP/TAZ blockade with vertical PI3K inhibition may benefit HPV-associated SNSCC, whereas targeting MYC and horizontal inhibition of RAS/PI3K may suit HPV-independent SNSCC. - Source: PubMed
Publication date: 2025/06/11
Zamuner Fernando TGunti SreenivasuluStarrett Gabriel JFaraji FarhoudToni TiffanySaraswathula AnirudhVu KennyGupta AnujZhang YanFaden Daniel LBryan Michael EGuo TheresaRowan Nicholas RRamanathan MurugappanLane Andrew PFakhry CaroleGallia Gary LAllen Clint TRooper Lisa MLondon Nyall R - Mechanisms of tumorigenesis in sinonasal squamous cell carcinoma (SNSCC) remain poorly described due to its rare nature. A subset of SNSCC are associated with the human papillomavirus (HPV); however, it is unknown whether HPV is a driver of HPV-associated SNSCC tumorigenesis or merely a neutral bystander. We hypothesized that performing the first large high-throughput sequencing study of SNSCC would reveal molecular mechanisms of tumorigenesis driving HPV-associated and HPV-independent SNSCC and identify targetable pathways. High-throughput sequencing was performed on 64 patients with HPV-associated and HPV-independent sinonasal carcinomas. Mutation annotation, viral integration, copy number, and pathway-based analyses were performed. Analysis of HPV-associated SNSCC revealed similar mutational patterns observed in HPV-associated cervical and head and neck squamous cell carcinoma, including lack of mutations and the presence of known hotspot mutations in PI3K and FGFR3. Further similarities included enrichment of APOBEC mutational signature, viral integration at known hotspot locations, and frequent mutations in epigenetic regulators. HPV-associated SNSCC-specific recurrent mutations were also identified including , , , , and . Mutations in and were associated with decreased overall survival. We developed the first known HPV-associated SNSCC cell line and combinatorial small molecule inhibition of YAP/TAZ and PI3K pathways synergistically inhibited tumor cell clonogenicity. In conclusion, HPV-associated SNSCC and HPV-independent SNSCC are driven by molecularly distinct mechanisms of tumorigenesis. Combinatorial blockade of YAP/TAZ and vertical inhibition of the PI3K pathway may be useful in targeting HPV-associated SNSCC whereas targeting MYC and horizontal inhibition of RAS/PI3K pathways for HPV-independent SNSCC. - Source: PubMed
Publication date: 2024/06/18
Zamuner Fernando TGunti SreenivasuluStarrett Gabriel JFaraji FarhoudToni TiffanySaraswathula AnirudhVu KennyGupta AnujZhang YanFaden Daniel LBryan Michael EGuo TheresaRowan Nicholas RRamanathan MurugappanLane Andrew PFakhry CaroleGallia Gary LAllen Clint TRooper Lisa MLondon Nyall R - High-grade serous ovarian carcinoma (HGSOC) is the most aggressive and prevalent subtype of ovarian cancer and accounts for a significant portion of ovarian cancer-related deaths worldwide. Despite advancements in cancer treatment, the overall survival rate for HGSOC patients remains low, thus highlighting the urgent need for a deeper understanding of the molecular mechanisms driving tumorigenesis and for identifying potential therapeutic targets. Whole-exome sequencing (WES) has emerged as a powerful tool for identifying somatic mutations and alterations across the entire exome, thus providing valuable insights into the genetic drivers and molecular pathways underlying cancer development and progression. - Source: PubMed
Publication date: 2024/04/12
Kong DeshuiWu YuLiu QiyuHuang CuiyuWang TongxiaHuang ZongyaoGao YanLi YuanGuo Hongyan - Host-virus interactions can significantly impact the viral life cycle and pathogenesis; however, our understanding of the specific host factors involved in highly pathogenic avian influenza A virus H7N9 (HPAI H7N9) infection is currently restricted. Herein, we designed and synthesized 65 small interfering RNAs targeting host genes potentially associated with various aspects of RNA virus life cycles. Afterward, HPAI H7N9 viruses were isolated and RNA interference was used to screen for host factors likely to be involved in the life cycle of HPAI H7N9. Moreover, the research entailed assessing the associations between host proteins and HPAI H7N9 proteins. Twelve key host proteins were identified: Annexin A (ANXA)2, ANXA5, adaptor related protein complex 2 subunit sigma 1 (AP2S1), adaptor related protein complex 3 subunit sigma 1 (AP3S1), ATP synthase F1 subunit alpha (ATP5A1), COPI coat complex subunit alpha (COP)A, COPG1, heat shock protein family A (Hsp70) member 1A (HSPA)1A, HSPA8, heat shock protein 90 alpha family class A member 1 (HSP90AA1), RAB11B, and RAB18. Co-immunoprecipitation revealed intricate interactions between viral proteins (hemagglutinin, matrix 1 protein, neuraminidase, nucleoprotein, polymerase basic 1, and polymerase basic 2) and these host proteins, presumably playing a crucial role in modulating the life cycle of HPAI H7N9. Notably, ANXA5, AP2S1, AP3S1, ATP5A1, HSP90A1, and RAB18, were identified as novel interactors with HPAI H7N9 proteins rather than other influenza A viruses (IAVs). These findings underscore the significance of host-viral protein interactions in shaping the dynamics of HPAI H7N9 infection, while highlighting subtle variations compared with other IAVs. Deeper understanding of these interactions holds promise to advance disease treatment and prevention strategies. - Source: PubMed
Publication date: 2024/03/19
Yu Dong-ShanWu Xiao-XinWeng Tian-HaoCheng Lin-FangLiu Fu-MinWu Hai-BoLu Xiang-YunWu Nan-PingSun Shui-LinYao Hang-Ping