ArticleOncogene2012
DNAJB6 chaperones PP2A mediated dephosphorylation of GSK3β to downregulate β-catenin transcription target, osteopontin.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
- DNAJB6 as an immuno-oncogenic hub in liver hepatocellular carcinoma: multi-omic profiling reveals prognostic significance and therapeutic vulnerability.Journal of molecular histology · 2026Article
- Protocadherin-7 Regulates Monocyte Migration Through Regulation of Small GTPase RhoA and Rac1.International journal of molecular sciences · 2025Article
- Review
- Article
- Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk.Genes & diseases · 2024Review
- Review
- Protein Phosphatase 2A as a Therapeutic Target in Pulmonary Diseases.Medicina (Kaunas, Lithuania) · 2023Review
- Article
- FAM122A Is Required for Mesendodermal and Cardiac Differentiation of Embryonic Stem Cells.Stem cells (Dayton, Ohio) · 2023Article
- Multi-Faceted Roles of DNAJB Protein in Cancer Metastasis and Clinical Implications.International journal of molecular sciences · 2022Review
- Regulation of p53 and Cancer Signaling by Heat Shock Protein 40/J-Domain Protein Family Members.International journal of molecular sciences · 2021Review
- Review of PP2A Tumor Biology and Antitumor Effects of PP2A Inhibitor LB100 in the Nervous System.Cancers · 2021Review
- DNAJB9 suppresses the metastasis of triple-negative breast cancer by promoting FBXO45-mediated degradation of ZEB1.Cell death & disease · 2021Article
- Inhibiting β-catenin disables nucleolar functions in triple-negative breast cancer.Cell death & disease · 2021Article
- GSK3 Inhibits Macropinocytosis and Lysosomal Activity through the Wnt Destruction Complex Machinery.Cell reports · 2020Article
- DNAJB6 Promotes Ferroptosis in Esophageal Squamous Cell Carcinoma.Digestive diseases and sciences · 2020Article
- Protein Phosphatase 2A Inhibiting β-Catenin Phosphorylation Contributes Critically to the Anti-renal Interstitial Fibrotic Effect of Norcantharidin.Inflammation · 2020Article
- Unravelling the Role of Glycogen Synthase Kinase-3 in Alzheimer's Disease-Related Epileptic Seizures.International journal of molecular sciences · 2020Review
- Neuromuscular Diseases Due to Chaperone Mutations: A Review and Some New Results.International journal of molecular sciences · 2020Review
- Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Elevated levels of the oncoprotein, osteopontin (OPN), are associated with poor outcome of several types of cancers including melanoma. We have previously reported an important involvement of DNAJB6, a member of heat-shock protein 40 (HSP40) family, in negatively impacting tumor growth. The current study was prompted by our observations reported here which revealed a reciprocal relationship between DNAJB6 and OPN in melanoma specimens. The 'J domain' is the most conserved domain of HSP40 family of proteins. Hence, we assessed the functional role of the J domain in activities of DNAJB6. We report that the J domain of DNAJB6 is involved in mediating OPN suppression. Deletion of the J domain renders DNAJB6 incapable of impeding malignancy and suppressing OPN. Our mechanistic investigations reveal that DNAJB6 binds HSPA8 (heat-shock cognate protein, HSC70) and causes dephosphorylation of glycogen synthase kinase 3β (GSK3β) at Ser 9 by recruiting protein phosphatase, PP2A. This dephosphorylation activates GSK3β, leading to degradation of β-catenin and subsequent loss of TCF/LEF (T cell factor1/lymphoid enhancer factor1) activity. Deletion of the J domain abrogates assembly of this multiprotein complex and renders GSK3β inactive, thus, stabilizing β-catenin, a transcription co-activator for OPN expression. Our in-vitro and in-vivo functional analyses show that silencing OPN expression in the background of deletion of the J domain renders the resultant tumor cells less malignant despite the presence of stabilized β-catenin. Thus, we have uncovered a new mechanism for regulation of GSK3β activity leading to inhibition of Wnt/β-catenin signaling.
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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.