IAP4 _ BIRC5 pThr34
- Known as:
- IAP4 _ BIRC5 pThr34
- Catalog number:
- AP10287PU-N
- Product Quantity:
- 0.1 mg
- Category:
- -
- Supplier:
- ACR
- Gene target:
- IAP4 _ BIRC5 pThr34
Related genes to: IAP4 _ BIRC5 pThr34
- Gene:
- BIRC5 NIH gene
- Name:
- baculoviral IAP repeat containing 5
- Previous symbol:
- API4
- Synonyms:
- EPR-1, survivin
- Chromosome:
- 17q25.3
- Locus Type:
- gene with protein product
- Date approved:
- 1998-06-10
- Date modifiied:
- 2016-10-04
Related products to: IAP4 _ BIRC5 pThr34
Related articles to: IAP4 _ BIRC5 pThr34
- Neuroblastoma is a pediatric solid malignancy that primarily arises from poorly differentiated sympathoadrenal cells in the developing autonomic nervous system. The neuroblastoma genetic landscape is characterized by a paucity of somatic mutations and a far more common occurrence of chromosome copy number variations (CNVs). Two of the most common genetic abnormalities in neuroblastoma are the amplification of MYCN and the unbalanced gain of the long arm of chromosome 17 (17q+), both of which correlate with poor prognosis. Although mouse models exist for MYCN-driven neuroblastoma, no mouse models exist for 17q+. Thus, the mechanism by which 17q+ contributes to poor prognosis remains largely unknown. Here, we used a human pluripotent stem cell (PSC) model of neuroblastoma to show that 17q+ cooperates with MYCN amplification to accelerate tumorigenesis compared to MYCN amplification alone. We identified six genes on 17q that are upregulated in both our 17q+ PSC-derived tumors and 17q+ neuroblastoma patient tumors compared to WT 17q, correlate with poor prognosis in neuroblastoma patients, and are overexpressed at the protein level in our MYCN/17q+ tumors compared to MYCN alone. Of these six genes, knockdown of BIRC5, CDC6, IGF2BP1, or TK1 in MYCN/17q+ cells increases tumor latency in vivo and contributes to tumor progression through diverse mechanisms. Furthermore, knockdown of CDC6, IGF2BP1, and TK1 in neuroblastoma patient-derived xenografts with 17q+ slowed growth in vivo. Our findings provide new insights into potential candidate 17q drivers of neuroblastoma tumorigenesis and possible therapeutic vulnerabilities. - Source: PubMed
Publication date: 2026/08/26
Fang WanqiCheng BoPastor StevenZobel Michael JPorras TaniaWu Hong-WeiKondapally TaneeshRoberts Stephen SParekh ChintanTsai Jessica WTsakiridis AnestisBarbaric IvanaAsgharzadeh ShahabMaris John MHuang Miller - Renal cell carcinoma (RCC) is a heterogeneous malignancy for which clear cell RCC (ccRCC) represents the most common and clinically aggressive subtype. Survivin (encoded by BIRC5), an inhibitor of apoptosis and key regulator of mitosis, is frequently overexpressed in RCC and associated with poor prognosis, yet its broader role in kidney cancer biology remains poorly defined. By analyzing transcriptomic data from The Cancer Genome Atlas-kidney renal clear cell carcinoma (TCGA-KIRC) cohort, we found that advanced-stage ccRCC exhibits widespread dysregulation of cell-cycle pathways, with 15,160 genes upregulated and 479 genes downregulated in stage IV compared to stage I tumors. To define survivin's functional contribution, we performed loss-of-function and pharmacologic inhibition studies in murine RENCA and human 786-O RCC cell lines. Survivin knockdown or treatment with the small-molecule inhibitor YM155 reduced proliferation, S-phase entry and cyclin D1 expression, and impaired collective (wound-healing), single-cell and transwell migration. Unexpectedly, survivin depletion increased mitochondrial content while lowering oxygen consumption, indicating accumulation of dysfunctional mitochondria. Together, these findings identify survivin as a node between cell-cycle progression and mitochondria in RCC. - Source: PubMed
Publication date: 2026/08/25
Tuli ShivaniInserra GabrielleMurakami YamatoVo CaisSenguttavan SarveshBae YonghoGau Dave - Unlike adult hearts, neonatal hearts can regenerate and adapt to stress. To identify both cardioprotective and regenerative mechanisms, we compared activated genes and related signaling pathways in the neonatal mouse heart after myocardial infarction (MI) and after exposure to pressure overload using a neonatal model of transverse aortic constriction (nTAC) at postnatal day 1 (P1). We identified three immune-related genes-Ccl4, S100a8, and C1qa-of high interest, as they encode secreted factors, are highly expressed in the neonatal mouse heart in both injury types, and their receptors are expressed on neonatal cardiomyocytes (nCM) and cardiac endothelial cells (EC). We investigated their effects on primary mouse EC and nCM in vitro. Our study found that the combination of these secreted factors (Pool3) enhances EC and nCM cell cycle re-entry and reduces the rate of apoptosis. Combined in vivo and in vitro transcriptome analyses revealed that Toll-like receptor 2 (TLR2) activation in nCM induces a shared pro-survival and cell cycle re-entry-associated signaling, including upregulation of Bcl2 and Birc5, respectively. The direct and pivotal role of TLR2 in enhancing nCM cell cycle re-entry and survival was further confirmed using TLR2 knockout (KO) nCM, a TLR2 inhibitor, and a TLR2 agonist (zymosan). Moreover, the importance of TLR2 in mediating the adaptive response to pressure overload in neonatal mice was confirmed in TLR2 KO mice, which failed to adapt to pressure overload and exhibited high mortality together with maladaptive cardiac remodeling as early as 7 days post-surgery. Collectively, these findings demonstrate that TLR2 is essential for mediating nCM cell cycle re-entry, survival, and adaptive/regenerative response to injury. - Source: PubMed
Publication date: 2026/08/14
Nicke JuliaGoldspink AdrianMenn MalteFleischmann Bernd KMalek Mohammadi Mona - Oral carcinoma is the sixth most prevalent cancer type with a poor 5-year survival rate. mRNA-lipid nanoparticle-based immunotherapy can overcome the challenges associated with conventional treatment options. Here, we investigated the immunogenicity and antitumor efficacy of survivin antigen encoded mRNA lipid nanoparticles (LNPs) in combination with anti-CTLA-4 immune checkpoint inhibitor. Survivin mRNA was synthesized by in vitro transcription technique after cloning the antigenic target sequence into an expression vector. The mRNA-LNPs were prepared with lipids, ALC-0315, DOPE, and cholesterol using a droplet-based microfluidic device. The average particle size, polydispersity index and encapsulation efficiency of mRNA-LNPs was found to be 305 ± 68 nm, 0.11, and 65 ± 3.9%, respectively. Survivin mRNA-LNPs incubated with mouse-derived bone marrow dendritic cells showed activation of tumor-associated antigen specific T-cells. The co-culture of splenocytes, and cheek cells derived from C57BL/6 mouse administered with survivin mRNA-LNPs and CTLA-4 inhibitor with MOC-1 oral carcinoma cells showed significant (P < 0.05) reduction in the cancer cell viability compared with control group. The oral cancer cytotoxicity is attributed to the upregulation of MHCI and MHCII, CD8 + and CD4 + T-lymphocytes and reduction in the T-regulatory cells. Taken together, this study provides preliminary evidence for further development of survivin mRNA-LNPs and CTLA-4 inhibitor combination for oral cancer immunotherapy. - Source: PubMed
Publication date: 2026/08/07
Krishna VandanaGoyal Srashti GopalVenuganti Venkata Vamsi Krishna - IntroductionFirst-generation EGFR-TKIs in NSCLC frequently lose efficacy as a result of the secondary EGFR-T790M mutation and a "persistent-STAT3" prosurvival pathway that sustains STAT3-survivin signaling in the face of EGFR inhibition. Preclinical evidence demonstrates that phytochemicals in the JI017 herbal formulation (2:1:1, : processed : ) can reinstate erlotinib sensitivity in T790M-positive NSCLC, and relevant molecular mechanisms have been examined.MethodsAnti-proliferative activities were evaluated in A549 (EGFR-WT), HCC827 (EGFR Δ19), and H1975 (EGFR L858R/T790M) cells utilizing MTT assays, colony formation, and Annexin V/7-AAD flow cytometry. Mechanistic analyses included immunoblotting for p-EGFR (Tyr1068/1173), p-JAK2, p-STAT3 (Tyr705), PARP, Bcl-2, survivin, and AXL, complemented by RT-qPCR for BIRC5 and AXL transcripts. Drug interaction effects were determined using the Chou-Talalay combination index (CompuSyn). Anti-tumor efficacy was assessed in H1975 xenografts treated for 14 days with vehicle, JI017, erlotinib, or combination therapy; tumors underwent H&E staining and IHC for p-STAT3, survivin, and Ki-67.ResultsJI017 inhibited proliferation in all NSCLC cell lines tested, showing greatest effectiveness in H1975, where it triggered PARP cleavage and suppression of Bcl-2 and survivin expression. In H1975, co-treatment with JI017 and erlotinib led to synergistic growth inhibition, eradicated colony growth, and significantly elevated apoptotic cell populations compared to single treatments. While erlotinib alone reduced p-EGFR and p-JAK2, it left p-STAT3 largely unaltered, reflecting persistent-STAT3 activity. The combination regimen abrogated p-STAT3, further lowered p-EGFR and p-JAK2 levels, diminished BIRC5 mRNA, and decreased both AXL protein and transcript levels. In vivo, the drug combination achieved sustained tumor stasis relative to controls or monotherapy; combination group tumors displayed widespread necrosis and substantial decreases in p-STAT3, survivin, and Ki-67.DiscussionThese data support the suppression of STAT3-survivin as the primary mechanism by which JI017 sensitizes EGFR-T790M models to erlotinib. The consistent down-regulation of AXL indicates the inhibition of an AXL-mediated bypass that may maintain STAT3 signaling during EGFR blockade, although causality has yet to be confirmed. The marked in-vivo tumor inhibition without observable toxicity underscores the translational promise as a low-toxicity therapeutic adjunct.ConclusionsJI017 restores erlotinib sensitivity in EGFR-T790M NSCLC by inhibiting STAT3-survivin signaling and possibly reducing AXL-mediated resistance, resulting in durable antitumor effects both in vitro and in vivo. Additional preclinical studies and early-phase clinical assessment of JI017 in combination with erlotinib are justified. - Source: PubMed
Publication date: 2026/08/04
Kim DaeunKim Young-HaChoi GaeunCheon ChunhooKo Seong-Gyu