Ask about this productRelated genes to: PDIA4 Blocking Peptide
- Gene:
- PDIA4 NIH gene
- Name:
- protein disulfide isomerase family A member 4
- Previous symbol:
- -
- Synonyms:
- ERP70, ERP72
- Chromosome:
- 7q36.1
- Locus Type:
- gene with protein product
- Date approved:
- 2005-03-02
- Date modifiied:
- 2016-10-05
Related products to: PDIA4 Blocking Peptide
Related articles to: PDIA4 Blocking Peptide
- Cystic fibrosis (CF) is a genetic disorder caused by CFTR mutations, most commonly ΔF508, leading to defective ion transport and multisystem pathology. Small-molecule modulators partially restore mutant CFTR function, but therapeutic efficacy remains limited, particularly for N1303K mutation refractory to current treatments. Here, we show that inhibition of the glutaminyl-peptide cyclotransferase (QPCT)-dependent pathway rescues both the surface expression and functional activity of ΔF508 CFTR. Integrated molecular and physiological analyses identify protein disulfide-isomerase A4 (PDIA4) as a key mediator of this process through a pyroglutamate (pGlu)-dependent association with misfolded ΔF508 CFTR. QPCT-dependent pGlu modification promotes the association of PDIA4 with mutant CFTR within the endoplasmic reticulum (ER) quality control machinery, whereas inhibition of QPCT disrupts this interaction, relieving ER retention and enabling a fraction of ΔF508 CFTR to reach the cell surface. Furthermore, inhibition of QPCT also restores the function of the N1303K CFTR mutant, indicating a broader relevance of this pathway in regulating CFTR proteostasis. These findings provide evidence for an ER quality control mechanism governing mutant CFTR fate and suggest potential therapeutic strategies for CFTR mutations that are unresponsive to existing modulators. - Source: PubMed
Publication date: 2026/06/09
Sun LeRodriguez LarryPankow SandraDiedrich JoleneQin KeZhang JiananWu XuWu PengYates John R - Aberrant cholesterol biosynthesis is a notable hallmark of cancers, supporting unlimited cell proliferation. Previously, we delineated that cholesterol synthases FDFT1 and SQLE promoted colorectal cancer (CRC) cell proliferation, while how these enzymes influence CRC metastasis and stemness remains unclear. This study demonstrates that suppress of FDFT1 or SQLE enhances CRC metastasis and stemness through impairing ER stress and degrading PDIA4 or SYVN1 individually. Additionally, the function of FDFT1 and SQLE on CRC metastasis relies on tryptophan. Tryptophan augments PDIA4-ACLY and SYVN1-SCD1 co-complex association to drive CRC metastasis and stemness. Consequently, the specific inhibitor of ACLY or SCD1 blocks FDFT1 or SQLE deficiency induced CRC metastasis using Male BALB/c nude mice. Besides, sub-cytotoxic concentrations of inhibitors targeting FDFT1 or SQLE generate the invasive feature in CRC cells. Overall, these findings indicate that cholesterol synthases impact ER homeostasis and fatty acid synthesis to regulate CRC metastasis and stemness, offering potential for combined targeted therapies in CRC. - Source: PubMed
Publication date: 2026/04/14
Li WenjieLin MoubinZhao YunTang YuqiChen YingHe Luwei - Triple-negative breast cancer (TNBC) exhibits addiction to chronic endoplasmic reticulum (ER) stress, which sustains an aggressive metastatic phenotype through activation of the unfolded protein response (UPR). Here, we identify a previously unrecognized "ER-stress addiction" axis in which the Hippo pathway effector TEAD4 directly transcriptionally upregulates the ER chaperone PDIA4. We further demonstrate that this axis can be pharmacologically targeted by a natural polysaccharide. Tetrastigma hemsleyanum polysaccharide (THP) selectively activates the Hippo kinase cascade, leading to YAP phosphorylation, cytoplasmic sequestration, and subsequent degradation. This cascade attenuates YAP/TEAD4 interaction and abolishes TEAD4 DNA-binding activity. Moreover, THP downregulates TEAD4 expression. These combined effects drive transcriptional suppression of PDIA4, catastrophic disruption of ER proteostasis, and ultimately lethal ER stress in TNBC cells. Functionally, THP inhibits migration, invasion, angiogenesis, and intracellular Ca flux in vitro, and-importantly-blocks metastasis in patient-derived organoids, zebrafish xenografts, and two syngeneic mouse models at non-toxic doses. Multi-omics analyses and rescue assays confirm the TEAD4-PDIA4 axis as the core functional module. Our findings establish THP as a first-in-class, natural-product-based therapeutic that disrupts ER-stress addiction in metastatic TNBC by targeting the Hippo-YAP/TEAD4-PDIA4 axis. - Source: PubMed
Publication date: 2026/04/02
Shang YiniSi WentaoZhang YouxueLiu JialinZhang HuaixiLi YafeiSu HongmengJiang WeiDing ZhishanWang Lihong - The transcriptomic effects of hybridization and triploidization were investigated in diploid and triploid rainbow trout, diploid brook trout, as well as triploid hybrids of rainbow trout and brook trout. The examined fish were reared under identical conditions for about two and a half years after hatching. Expression of ten genes involved in cellular respiration (, ), mitochondrial functioning (, ), ribosome biogenesis (, ), proteasome-mediated protein turnover (, ), and protein chaperoning (, ) was studied in liver and muscle tissues. Most of the analyzed genes (, , , , , , and ) displayed comparable expression levels in the liver tissue across the examined triploid hybrids and diploid parental species, with stabilization of genes that were both positively and negatively compensated in the triploid rainbow trout. In turn, significant upregulation of , , and genes, together with downregulation of gene, was observed in the triploid rainbow trout liver and muscle, respectively. On the other hand, triploid hybrids showed marked transcriptional upregulation of genes primarily associated with energy metabolism and protein synthesis (, , , and ) relative to all the fish groups examined. Although protein-synthesis- and energy-related genes were upregulated in the muscles of triploid hybrids, the recorded growth performance data did not indicate clear evidence of growth heterosis (MPH = -14.3% for body weight; MPH = -0.4% for body length), suggesting that potential benefits of increased heterozygosity in this cross may not be fully reflected in enhanced growth. Three- to four-fold downregulation of the heat shock protein () gene was also observed in both tissues of triploid hybrids compared with purebred diploid and triploid trout, which may reflect potential maladaptive genomic effects commonly observed in distant salmonid crosses, suggesting altered stress-response regulation in the examined triploid hybrids. - Source: PubMed
Publication date: 2026/03/17
Kuciński MarcinRożyński RafałOcalewicz Konrad - Microsporidia are known intracellular pathogens that infect nearly all animals and deeply manipulate host mitochondrial homeostasis for survival. Here, we report a novel mechanism by which the human-pathogenic Encephalitozoon hellem modulates the mitophagy machinery of its host. We identified the secreted protein EhPTP4 as a key effector in disrupting selective degradation processes in the infected cells. EhPTP4 is found to localize within the nucleus of infected cells, where it induces increased expression of endoplasmic reticulum-associated degradation (ERAD) pathway components, including HSPA5, HERPUD1, and PDIA4. This induction enhances protein ubiquitination in host cells and leads to the degradation of BNIP3L, a critical regulator of mitophagy. Investigation into the molecular interaction network revealed that EhPTP4 interacts with host corepressor RCOR1 and histone H3. This interaction modulates histone acetylation, specifically at H3K14ac sites, thereby further influencing the expression of a key ERAD gene, HERPUD1. This study uncovers a sophisticated strategy by which microsporidia manipulates both ER stress response and the histone acetylation to suppress mitophagy. These findings provide new insights into the mechanisms of microsporidian pathogenesis. - Source: PubMed
Publication date: 2026/03/23
Zou ZiyunHu YiboGuan ZhongxiaChen JiajingZhang QingyaoHan YinzeZhu JunyuWang ChunxiaHan BingLi TianZhou Zeyang