ArticleThe Journal of biological chemistry2019
The RING domain in the anti-apoptotic protein XIAP stabilizes c-Myc protein and preserves anchorage-independent growth of bladder cancer cells.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Oncogene c‑Myc: From molecular mechanism to targeted therapy (Review).Molecular medicine reports · 2026Review
- X-Linked Inhibitor of Apoptosis Protein (XIAP) Contributes to ERK1/2-Mediated Anoikis Resistance in Hepatocellular Carcinoma.MedComm - Oncology · 2026Article
- The urothelial gene regulatory network: understanding biology to improve bladder cancer management.Oncogene · 2024Review
- Hyaluronan-CD44 Interaction Regulates Mouse Retinal Progenitor Cells Migration, Proliferation and Neuronal Differentiation.Stem cell reviews and reports · 2023Article
- Lentiviral Gene Transfer Corrects Immune Abnormalities in XIAP Deficiency.Journal of clinical immunology · 2023Article
- The Superior Cytotoxicity of Dual Targeting of BCR/ABL and PI3K in K562 Cells: Proposing a Novel Therapeutic Potential for the Treatment of CML.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2022Article
- Subcellular localization of X-linked inhibitor of apoptosis protein (XIAP) in cancer: Does that matter?BBA advances · 2022Review
- PTPN18 promotes colorectal cancer progression by regulating the c-MYC-CDK4 axis.Genes & diseases · 2021Article
- XIAP's Profile in Human Cancer.Biomolecules · 2020Review
- TCF21: a critical transcription factor in health and cancer.Journal of molecular medicine (Berlin, Germany) · 2020Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
X-linked inhibitor of apoptosis protein (XIAP) suppresses apoptosis and plays key roles in the development, growth, migration, and invasion of cancer cells. Therefore, XIAP has recently attracted much attention as a potential antineoplastic therapeutic target, requiring elucidation of the molecular mechanisms underlying its biological activities. Here, using shRNA-mediated gene silencing, immunoblotting, quantitative RT-PCR, anchorage-independent growth assay, and invasive assay, we found that XIAP's RING domain, but not its BIR domain, is crucial for XIAP-mediated up-regulation of c-Myc protein expression in human bladder cancer (BC) cells. Mechanistically, we observed that the RING domain stabilizes c-Myc by inhibiting its phosphorylation at Thr-58 and that this inhibition is due to activated ERK1/2-mediated phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser-9. Functional studies further revealed that c-Myc protein promotes anchorage-independent growth and invasion stimulated by the XIAP RING domain in human BC cells. Collectively, the findings in our study uncover that the RING domain of XIAP supports c-Myc protein stability, providing insight into the molecular mechanism and role of c-Myc overexpression in cancer progression. Our observations support the notion of targeting XIAP's RING domain and c-Myc in cancer therapy.
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