An Qin Similar Datasets
Project description:Heterozygous in-frame mutations in coding regions of human STAT3 underlie the only known autosomal dominant form of hy- per IgE syndrome (AD HIES). About 5% of familial cases remain unexplained. The mutant proteins are loss-of-function and dominant-negative when tested following overproduction in re- cipient cells. However, the production of mutant proteins has not been detected and quantified in the cells of heterozygous pa- tients. We report a deep intronic heterozygous STAT3 mutation, c.1282-89C>T, in 7 relatives with AD HIES. This mutation creates a new exon in the STAT3 complementary DNA, which, when over- expressed, generates a mutant STAT3 protein (D427ins17) that is loss-of-function and dominant-negative in terms of tyrosine phos- phorylation, DNA binding, and transcriptional activity. In immor- talized B cells from these patients, the D427ins17 protein was 2 kDa larger and 4-fold less abundant than wild-type STAT3, on mass spectrometry. The patients’ primary B and T lymphocytes responded poorly to STAT3-dependent cytokines. These findings are reminiscent of the impaired responses of leukocytes from other patients with AD HIES due to typical STAT3 coding muta- tions, providing further evidence for the dominance of the mutant intronic allele. These findings highlight the importance of sequenc- ing STAT3 introns in patients with HIES without candidate variants in coding regions and essential splice sites. They also show that AD HIES-causing STAT3 mutant alleles can be dominant-negative even if the encoded protein is produced in significantly smaller amounts than wild-type STAT3.
2020-04-30 | GSE149602 | GEO
Project description:Many patients have cancers that have increased activity of a protein called STAT3 that contributes critically to the development and growth of their cancer. Despite our knowledge of STAT3’s importance to cancer, scientists and doctors have not developed a drug that targets it and that patients can take to treat their cancer more effectively than treatments that are now available. Tvardi Therapeutics, Incorporated has developed a compound, TTI-101, which can be given by mouth and acts as a direct inhibitor of STAT3. Administration of TTI-101 to mice demonstrated that it blocked growth of cancers of the breast, head and neck, lung, and liver and it was safe when administered at high doses to mice, rats, and dogs. In this application, Tvardi is proposing to further develop TTI-101 for treatment of solid tumors for which the prognosis is dismal. The investigators will determine how safe it is when administered to patients with cancer, determine whether an adequate dose can be administered to patients with cancer that will block STAT3 in their cancer, and determine whether treatment with TTI-101 leads to reduced growth of their cancer.
| 2247646 | ecrin-mdr-crc
Project description:Mass spectrometry analysis of proteins interacting with STAT3¬Flag was performed. STAT3-Flag was transiently expressed in HeLa cells and the interactome of STAT3-Flag was studied in lysosomal extracts. proteins co-¬immunoprecipitating with STAT3--Flag identified eight subunits of the vacuolar H+-¬ ATPase (V-¬ATPase) as potential STAT3 binding partners. Validation experiments were performed by antibody pull-down of STAT3.
2018-08-29 | PXD006788 | Pride
Project description:Human embryonic stem cells (hESCs) are isolated from the inner cell mass of the blastocysts. The pluripotent properties of hESCs enable the derivation of cell-types or tissues of different lineages for potential applications such as therapeutics discovery and regenerative medicine. Even though hESCs are pluripotent, differences have been observed when compared to the native pluripotent epiblast cells of the blastocyst. We use a chemical approach (3iL: 3 small molecule inhibitor and cytokine) to induce an expression signature that more closely resembles native pluripotent cells. This experiment is STAT3 binding data in 3iL hESCs.
2013-12-05 | E-MTAB-2042 | biostudies-arrayexpress
Project description:Renal cell carcinoma (RCC) is a common urinary malignancy. It has the highest mortality rate among urologic malignancies, and its incidence has been increasing in recent years, and its common subtype is renal clear cell carcinoma (ccRCC). Ovarian tumor domain protease 1 (OTUD1) is known as a member of the OTUD deubiquitinase family and has the ability to remove ubiquitin modifications from target proteins. The OTUD family consists of 10 members, including OTUD1, all of which have the function of deubiquitinating target proteins. In this study, we determined the correlation between OTUD1 and the immune pathway through bioinformatics analysis. Subsequently, by mass spectrometry analysis and immunoprecipitation experiments, we demonstrated that OTUD1 can interact with STAT3 and regulate the expression of PD-L1 in kidney cancer cells through STAT3. OTUD1 can also inhibit the activity and nuclear translocation of STAT3 by regulating the K63 ubiquitination modification of STAT3. Finally, we found that OTUD1 can deubiquitinate STAT3 and inhibit its activity and nuclear translocation, thereby regulating the PD-1 signaling pathway, and ultimately promoting the immune response of renal cancer tumors.
2025-12-02 | GSE249822 | GEO
Project description:Overexpression of HIP1 has been associated with fibroblast transformation, increasing grades of prostate cancer (CaP), and biochemical relapse. Here we demonstrate cellular transformation and phenotypic effects of HIP1 overexpression in a benign prostate epithelial cell line to be dependent on STAT3 signalling. In vivo xenografts confirmed the cellular transformation phenotype and revealed serum GDF15 to be a marker of CaP in our model. STAT3 signalling was in part, dependent on HIP1 expression, in a highly invasive, metastatic and androgen receptor (AR) negative DU145 cell line, Immunohistochemistry of a large prostate tissue microarray (TMA) revealed increased HIP1 and reciprocal GDF15 expression to adversely affect outcome warranting further studies to assess HIP1 and GDF15 as biomarkers for detection and prognostication of CaP. Gene expression of PNT1a cells stably overexpressing HIP1 protein and LNCaP cells transiently overexpressing HIP1 protein were compared with their respective empty vector control cell lines using the illumina expression array platform. There were six biological replicates for each of the four different groups.
2016-09-01 | E-GEOD-35211 | biostudies-arrayexpress
Project description:Purification of mouse mRNAs encoding signal transducer and activator of transcription 3 (Stat3) identified many miRNAs using multiplex miRNA array in RAW264.7 cells. To investigate the miRNAs targeting to mouse Stat3 gene in macrophage cells, we performed a protocol miRIP to affinity purify the miRNAs from an endogenous segment of Stat3 mRNA using nucleic acid hybridization and use multiplex miRNA array to identify the associated miRNAs.
2016-02-13 | E-GEOD-77873 | biostudies-arrayexpress
Project description:Activation of Signal Transducer and Activator of Transcription 3 (STAT3) is common in prostate cancers. STAT3 may induce cell proliferation and resistance to apoptosis, as well as promote tumor angiogenesis, invasion, and migration by activating gene expression. Many STAT3-dependent transcriptional responses are mediated through protein-protein interactions that involve the amino-terminal domain (N-domain). In this study, we found that inhibition of the STAT3 N-domain using novel inhibitor ST3-Hel2A-2 induces apoptotic death in prostate cancer cells. The cell death was accomponied by robust activation of pro-apoptotic gene. Using chromatin immunoprecipitation and tiling human promoter arrays (ChIP-chip), we have defined genome-wide targets of STAT3 in DU145 prostate cancer cells. We found that upregulated pro-apoptotic genes were bound by STAT3 in prostate cancer cells, and that STAT3 binding was decreased following inhibition of the STAT3 N-domain. STAT3 siRNA knockdow confirmed specificity of STAT3 binding and changes in gene expression. DU145 cells were treated with STAT3 siRNA or scrambled siRNA for 48hr. Total RNA has been extracted and prepared for hybridization on Affymetrix HG-U133A 2.0 arrays.
2010-12-07 | E-GEOD-25867 | biostudies-arrayexpress
Project description:Herpes simplex virus type 1 (HSV-1) is the prototype of the α-herpesvirus family. To propagate within the host organism, HSV-1 has evolved several strategies to subvert the host immune response. Due to the pivotal role of dendritic cells (DCs), bridging innate and adaptive immunity and activating naïve T cells, they represent an attractive target for HSV-1-triggered immune regulation. Here, we report a novel HSV-1-mediated mechanism of signal transducer and activator of transcription 3 (STAT3) dysregulation in human monocyte-derived mature DCs (mDCs). Due to STAT3’s antiviral activity, STAT3 was shown to be modulated by viruses to efficiently replicate in several different cell types, however, not in DCs. We show that HSV-1 infection of mDCs leads to diminished total STAT3 expression and STAT3 phosphorylation (pSTAT3), as well as downregulation of STAT3 mRNA very early upon infection. Protein downregulation of STAT3 could be verified by label-free mass spectrometric analysis of HSV-1- and HSV-2-infected mDCs. We found that two viral proteins, the tegument protein virion host shutoff (vhs) and the immediate early (IE) protein ICP27, contribute to STAT3 protein downregulation upon HSV-1 infection. However, HSV-1 Δvhs and ΔICP27 deletion strains still inhibited pSTAT3 in infected mDCs, suggesting that different viral proteins impair STAT3 phosphorylation and total STAT3. Moreover, STAT3 protein levels were degraded in a proteasome-dependent, but apoptosis-independent manner. Taken together, we demonstrate that HSV-1 downregulates STAT3 in HSV-1-infected human mDCs at the transcript, protein and phosphorylation levels. Downregulation of STAT3 protein depended on vhs and the proteasome, very likely to shape DC function for immune evasion and modulation.
2026-07-23 | PXD081503 | Pride