ArticleThe Journal of clinical investigation2016
Endogenous transmembrane protein UT2 inhibits pSTAT3 and suppresses hematological malignancy.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- ARMH4 accelerates aging by maintaining a positive-feedback growth signaling circuit.Nature communications · 2025Article
- 27-Hydroxycholesterol Negatively Affects the Function of Bone Marrow Endothelial Cells in the Bone Marrow.International journal of molecular sciences · 2024Article
- Identification of ARMH4 and WIPF3 as human podocyte proteins with potential roles in immunomodulation and cytoskeletal dynamics.PloS one · 2023Article
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- Transcriptomic Biomarker Signatures for Discrimination of Oral Cancer Surgical Margins.Biomolecules · 2022Article
- Identification of Hub Genes Associated With Clear Cell Renal Cell Carcinoma by Integrated Bioinformatics Analysis.Frontiers in oncology · 2021Article
- Armadillo-like helical domain containing-4 is dynamically expressed in both the first and second heart fields.Gene expression patterns : GEP · 2019Article
- OKN-007 Increases temozolomide (TMZ) Sensitivity and Suppresses TMZ-Resistant Glioblastoma (GBM) Tumor Growth.Translational oncology · 2019Article
- Role of STAT3 in Genesis and Progression of Human Malignant Gliomas.Molecular neurobiology · 2017Review
- DNMT3B overexpression contributes to aberrant DNA methylation and MYC-driven tumor maintenance in T-ALL and Burkitt's lymphoma.Oncotarget · 2017Article
- Regulation of normal and leukemic stem cells through cytokine signaling and the microenvironment.International journal of hematology · 2017Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Regulation of STAT3 activation is critical for normal and malignant hematopoietic cell proliferation. Here, we have reported that the endogenous transmembrane protein upstream-of-mTORC2 (UT2) negatively regulates activation of STAT3. Specifically, we determined that UT2 interacts directly with GP130 and inhibits phosphorylation of STAT3 on tyrosine 705 (STAT3Y705). This reduces cytokine signaling including IL6 that is implicated in multiple myeloma and other hematopoietic malignancies. Modulation of UT2 resulted in inverse effects on animal survival in myeloma models. Samples from multiple myeloma patients also revealed a decreased copy number of UT2 and decreased expression of UT2 in genomic and transcriptomic analyses, respectively. Together, these studies identify a transmembrane protein that functions to negatively regulate cytokine signaling through GP130 and pSTAT3Y705 and is molecularly and mechanistically distinct from the suppressors of cytokine signaling (SOCS) family of genes. Moreover, this work provides evidence that perturbations of this activation-dampening molecule participate in hematologic malignancies and may serve as a key determinant of multiple myeloma pathophysiology. UT2 is a negative regulator shared across STAT3 and mTORC2 signaling cascades, functioning as a tumor suppressor in hematologic malignancies driven by those pathways.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.