ArticleThe EMBO journal2017
USP49 negatively regulates tumorigenesis and chemoresistance through FKBP51-AKT signaling.
Article in The EMBO journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 101 citations in OpenAlex.
- Rewiring KRAS-driven cancers through the ubiquitin-proteasome system: therapeutic opportunities with a focus on deubiquitinase.Experimental & molecular medicine · 2026Review
- PHLPP is neither a Phosphatase nor a Tumor Suppressor.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Ubiquitin-Specific Protease 49 Interacts with Bax to Modulate Apoptosis.International journal of molecular sciences · 2026Article
- USP25 aggravates liver cancer development and impairs chemosensitivity by limiting LATS1 activation.EMBO reports · 2026Article
- Targeting the UFL1-AKT cascade suppresses triple-negative breast cancer progression.Nature communications · 2026Article
- Deubiquitomic and bioinformatic analyses in cisplatin-treated lung cancer cells.International journal of medical sciences · 2026Article
- FK506‑binding proteins as emerging bridges linking proteostasis to multi‑system pathogenesis and therapeutic strategies (Review).International journal of molecular medicine · 2026Review
- FKBP5 Regulates Osteogenesis of Human iPSC-Derived Mesenchymal Stem Cells via FKBP5-AKT-FOXO1 Pathway.Journal of cellular and molecular medicine · 2025Article
- The multifaceted roles of deubiquitinating enzymes (DUBs) in pancreatic ductal adenocarcinoma.Cell death & disease · 2025Review
- Lactylation-induced ALKBH5 targets RNF123 to worsen retinal Müller cell activation through PKM2-regulated Glycolysis in diabetic retinopathy.Journal of translational medicine · 2025Article
- Psychological stress-induced systemic corticosterone directly sabotages intestinal stem cells and exacerbates colitis.Cell discovery · 2025Article
- Article
- FBXO2 promotes hepatocellular carcinoma progression and sorafenib resistance by targeting USP49 for proteasomal degradation.Frontiers in immunology · 2025Article
- IGF2BP3-dependent N6-methyladenosine modification of USP49 promotes carboplatin resistance in retinoblastoma by enhancing autophagy via regulating the stabilization of SIRT1.The Kaohsiung journal of medical sciences · 2024Article
- USP25 Elevates SHLD2-Mediated DNA Double-Strand Break Repair and Regulates Chemoresponse in Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Development of Chromatin Regulator-related Molecular Subtypes and a Signature to Predict Prognosis and Immunotherapeutic Response in Head and Neck Squamous Cell Carcinoma.Current cancer drug targets · 2024Article
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- USP49 deubiquitinase regulates the mitotic spindle checkpoint and prevents aneuploidy.Cell death & disease · 2023Article
- Ubiquitin signaling in pancreatic ductal adenocarcinoma.Frontiers in molecular biosciences · 2023Review
- USP17L2-SIRT7 axis regulates DNA damage repair and chemoresistance in breast cancer cells.Breast cancer research and treatment · 2022Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
The AKT pathway is a fundamental signaling pathway that mediates multiple cellular processes, such as cell proliferation and survival, angiogenesis, and glucose metabolism. We recently reported that the immunophilin FKBP51 is a scaffolding protein that can enhance PHLPP-AKT interaction and facilitate PHLPP-mediated dephosphorylation of AKT at Ser473, negatively regulating AKT activation. However, the regulation of FKBP51-PHLPP-AKT pathway remains unclear. Here we report that a deubiquitinase, USP49, is a new regulator of the AKT pathway. Mechanistically, USP49 deubiquitinates and stabilizes FKBP51, which in turn enhances PHLPP's capability to dephosphorylate AKT Furthermore, USP49 inhibited pancreatic cancer cell proliferation and enhanced cellular response to gemcitabine in a FKBP51-AKT-dependent manner. Clinically, decreased expression of USP49 in patients with pancreatic cancer was associated with decreased FKBP51 expression and increased AKT phosphorylation. Overall, our findings establish USP49 as a novel regulator of AKT pathway with a critical role in tumorigenesis and chemo-response in pancreatic cancer.
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Registered trials
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.