Ask about this productRelated genes to: PDPK1 antibody
- Gene:
- PDPK1 NIH gene
- Name:
- 3-phosphoinositide dependent protein kinase 1
- Previous symbol:
- -
- Synonyms:
- PDK1
- Chromosome:
- 16p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 1998-03-23
- Date modifiied:
- 2015-08-25
Related products to: PDPK1 antibody
Related articles to: PDPK1 antibody
- Intestinal ischemia/reperfusion (I/R) causes epithelial oxidative injury, barrier dysfunction, and apoptotic loss, yet its post-translational basis remains poorly understood. SUMOylation is a reversible post-translational process that modulates protein stability and intracellular signaling under stress. However, the role and mechanism of SENP3, a redox-sensitive deSUMOylase, in intestinal I/R remain unclear. In this study, we examined the contribution of SENP3 to intestinal I/R and its mechanism. SENP3 abundance increased substantially in intestinal tissue of mice subjected to I/R and epithelial cells subjected to hypoxia/reoxygenation (H/R). Moreover, blockade of hydrogen peroxide signaling reduced the H/R-induced increase in SENP3 protein without materially altering its mRNA level, suggesting peroxide-associated redox-dependent regulation primarily at the post-transcriptional level. Functionally, SENP3 knockdown alleviated mucosal injury, reduced epithelial apoptosis, and mitigated remote organ damage. Transcriptomic profiling revealed enrichment of the PI3K-Akt pathway following SENP3 knockdown. Additionally, PDPK1, a critical regulator of this pathway, was identified as a SENP3-interacting protein by immunoprecipitation-mass spectrometry and validated by co-immunoprecipitation. SENP3 promoted PDPK1 deSUMOylation in a catalytically dependent manner, leading to increased K48-linked ubiquitination and proteasomal degradation. Site-directed mutagenesis identified Lys296 as a major SUMOylation site on PDPK1. Consequently, SENP3-mediated PDPK1 destabilization suppressed PI3K-Akt signaling, whereas SENP3 inhibition preserved PDPK1 levels and downstream survival signaling. These findings support a SUMO-ubiquitin switch mechanism whereby SENP3-mediated deSUMOylation facilitates ubiquitin-dependent degradation of PDPK1. Overall, our findings define a SENP3-PDPK1-PI3K-Akt regulatory axis linking oxidative stress to epithelial apoptosis during intestinal I/R and support SENP3 as a candidate target for maintaining barrier integrity and reducing reperfusion-related injury. - Source: PubMed
Publication date: 2026/05/14
Liu RenwuLuan QinrongTian Xiaofeng - TNF α inhibitors such as adalimumab are widely used for autoimmune diseases, yet their long-term impact on tumor development in genetically susceptible individuals remains incompletely defined. Glioblastoma (GBM) is an aggressive IDH wild-type tumor with recurrent molecular alterations; however, comprehensive genomic analyses of GBM arising in patients treated with TNF-α inhibitors are extremely limited. We examined the genomic features of a GBM developing after prolonged TNF-α inhibitor therapy to explore potential links between TNF-α blockade, and tumor evolution. Tumor tissue was analyzed using immunohistochemistry, targeted next-generation sequencing, and copy number analysis performed at two independent clinical laboratories. Genomic findings were interpreted in the context of TNF α pathway biology and tumor microenvironment interactions relevant to GBM progression. The tumor demonstrated GFAP and OLIG positivity, a Ki-67 index of 45%, and strong p53 expression (>90%). Genomic profiling revealed hallmark alterations of IDH wild-type GBM, including CDKN2A/B deletions, PTEN deletion, and a TP53 mutation. Additional findings included a KDM6A frameshift variant, an ATRX variant of uncertain significance, and loss of PDPK1. No TERT promoter mutation was detected, suggesting a potential alternative telomere maintenance mechanism. The combination of PTEN loss, TP53 mutation, and CDKN2A/B deletion is consistent with an aggressive molecular phenotype associated with immune evasion. This case highlights genomic features of an IDH-wild-type glioblastoma arising after prolonged TNF-α inhibitor exposure. While no causal inference can be made, this analysis identifies both canonical and atypical genomic alterations in a GBM arising after prolonged TNF-α targeted therapy. This temporal relationship provides a basis for studying possible convergence between TNF-α signaling and GBM-associated pathways, and underscores the importance of genomic risk stratification when considering TNF-α inhibitor therapy. - Source: PubMed
Publication date: 2026/04/28
Mohapatra SuryanarayanGanesan Natarajan - Osteoporosis is a major global health challenge, particularly among aging populations, underscoring the need for safe and effective nutritional interventions. Probiotics and their metabolites have emerged as promising candidates for modulating bone health via the gut-bone axis. In this study, we investigated the effects of a cell-free culture supernatant (CFS) from the food-grade bacterium GBE18 on the proliferation, differentiation, and mineralization of MC3T3-E1 pre-osteoblasts. GBE18 CFS exhibited no cytotoxicity at concentrations ranging from 1% to 4% (/). Notably, 2% (/) CFS significantly enhanced alkaline phosphatase (ALP) activity and extracellular matrix mineralization ( < 0.05). Transcriptomic profiling revealed that differentially expressed genes were enriched in osteoblast-related processes and two key signaling pathways: Wnt/β-catenin and PI3K/Akt. Subsequent qRT-PCR and Western blot analyses confirmed the upregulation of critical regulators (, , ) and demonstrated coordinated activation of Akt phosphorylation, β-catenin stabilization, and Runx2 protein expression. Our findings indicate that GBE18 CFS promotes osteogenic differentiation through coordinated modulation of the PI3K/Akt and Wnt/β-catenin pathways. Consequently, this study provides mechanistic evidence supporting the potential application of GBE18-derived metabolites as functional food ingredients or dietary interventions for bone health and osteoporosis management. - Source: PubMed
Publication date: 2026/04/13
Peng XingyuanZheng XuanLi XiyuPang XiaonaJin JunhuaLiu HuiZhang HongxingXie Yuanhong - Prostate cancer (PCa) is the second most common cancer in men and shows high inter- and intra-patient heterogeneity. Consequently, treatment options are limited and there is a lack of representative preclinical models. Here, we establish a comprehensive biobank of murine organoids and tumoroids that reflect common patient mutations. We demonstrate that the deletion of Pten alone, or in combination with Stat3, or Tp53, drives the activation of cancer-related pathways in both prostate organoids and tumor-derived tumoroids. A medium-throughput drug screen identified two potent compounds, the PDPK1/AKT/FLT dual pathway inhibitor and the sirtuin inhibitor tenovin-6, which effectively suppressed tumoroid proliferation. Notably, these compounds also inhibited the growth of several human PCa cell lines and displayed synergistic effects when combined with the standard-of-care antiandrogen enzalutamide. Together, our findings provide evidence that murine tumoroids are versatile preclinical models for studying PCa tumorigenesis and drug sensitivities to develop therapeutic options for PCa patients. - Source: PubMed
Publication date: 2026/03/30
Kalla JessicaDillinger ThomasPavlovicova ZlataJacob ReemaAtas EmineMišura KatarinaBaskan AnilDraganić KristinaTiefenbacher AndreasLimberger TanjaMair TheresiaWasinger GabrielVillanti LudovicaKubicek StefanKenner LukasEgger Gerda - Radiotherapy resistance (RT resistance) remains a major obstacle in lung adenocarcinoma (LUAD) treatment, with dysregulated apoptosis being a key contributor. This study aim to investigate the role of PDPK1 in RT resistance in LUAD and its molecular mechanism. RT-resistant sublines (A549R/PC9R) were established via fractionated irradiation. Bioinformatic analysis (GSE197236 dataset) was performed to identify differentially expressed genes (DEGs). RNA sequencing, qPCR, ChIP, and dual-luciferase assays were conducted to elucidate the underlying mechanism. Cell viability, colony formation, and apoptosis were performed to functional validation. Results showed that PDPK1 was significantly upregulated in RT-resistant cells. PDPK1 knockdown inhibited cell viability and colony formation while promoting apoptosis in A549R and PC9R cells. Mechanistically, PDPK1 activated NFKB1, which in turn transactivated BIRC3, a key anti-apoptotic protein. BIRC3 overexpression reversed the pro-apoptotic effects of PDPK1 knockdown, restoring cell survival. These findings establish the PDPK1/NFKB1/BIRC3 signaling axis as a critical driver of RT resistance in NSCLC. In conclusion, our study reveals a novel molecular mechanism by which PDPK1 mediates RT resistance through the NFKB1/BIRC3 axis. Targeting this signaling pathway may represent a promising strategy to overcome RT resistance in LUAD. - Source: PubMed
Publication date: 2026/03/20
Shao HuapingXu KanLiu Yi