ArticleNature communications2023
Structural mechanism for inhibition of PP2A-B56α and oncogenicity by CIP2A.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Prenatal Characterization of Houge-Janssens Syndrome Type 2: A Case Report and Systematic Review of Fetal Phenotypes Associated With PPP2R1A Mutations.Molecular genetics & genomic medicine · 2025Pooled it
- Mechanisms of phosphorylation in colitis regulation: PP2Acα as an emerging therapeutic target for inflammatory bowel disease.Molecular biology reports · 2026Review
- Biomimetic PD-1 macrophage nanoplatform for Cip2a silencing and immune activation in oral squamous cell carcinoma.Journal of nanobiotechnology · 2026Article
- Computational identification and evaluation of curcumin derivatives as potential inhibitors of PPP2R5B to enhance insulin sensitivity.Scientific reports · 2026Article
- Fusion oncoproteins orchestrate tumorigenesis and sustain malignant progression via a positive feedback mechanism.Cell & bioscience · 2026Review
- Protein phosphatase 2A (PP2A) function in male germ cells and its importance for male fertility.Endocrine connections · 2025Review
- UCHL1 Promotes Gastric Cancer Progression by Regulating CIP2A Degradation.Pharmaceuticals (Basel, Switzerland) · 2025Article
- The Emerging Role of the Cancerous Inhibitor of Protein Phosphatase 2A in Pulmonary Diseases.Medicina (Kaunas, Lithuania) · 2025Review
- A PP2A-mtATR-tBid axis links DNA damage-induced CIP2A degradation to apoptotic dormancy and therapeutic resistance in PDAC.Cancer letters · 2025Article
- An Aurora kinase A-BOD1L1-PP2A B56 axis promotes chromosome segregation fidelity.Cell reports · 2025Article
- Mutant PP2A Induces IGFBP2 Secretion to Promote Development of High-Grade Uterine Cancer.Cancer research · 2025Article
- KRAS-mediated upregulation of CIP2A promotes suppression of PP2A-B56α to initiate pancreatic cancer development.Oncogene · 2024Article
- Novel PP2A-Activating Compounds in Neuroblastoma.Cancers · 2024Article
- PP2A activation overcomes leptomeningeal dissemination in group 3 medulloblastoma.The Journal of biological chemistry · 2024Article
- Article
- Helicobacter Pylori-Enhanced hnRNPA2B1 Coordinates with PABPC1 to Promote Non-mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- KRAS-mediated upregulation of CIP2A promotes suppression of PP2A-B56α to initiate pancreatic cancer development.bioRxiv : the preprint server for biology · 2024Article
- Emerging Roles of B56 Phosphorylation and Binding Motif in PP2A-B56 Holoenzyme Biological Function.International journal of molecular sciences · 2024Review
- An Aurora kinase A-BOD1L1-PP2A B56 Axis promotes chromosome segregation fidelity.bioRxiv : the preprint server for biology · 2024Article
- CIP2A induces PKM2 tetramer formation and oxidative phosphorylation in non-small cell lung cancer.Cell discovery · 2024Article
Corrections and comments
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Authors and funding
22 authors at 10 institutions in 8 countries.
Funding
Abstract
The protein phosphatase 2A (PP2A) heterotrimer PP2A-B56α is a human tumour suppressor. However, the molecular mechanisms inhibiting PP2A-B56α in cancer are poorly understood. Here, we report molecular level details and structural mechanisms of PP2A-B56α inhibition by an oncoprotein CIP2A. Upon direct binding to PP2A-B56α trimer, CIP2A displaces the PP2A-A subunit and thereby hijacks both the B56α, and the catalytic PP2Ac subunit to form a CIP2A-B56α-PP2Ac pseudotrimer. Further, CIP2A competes with B56α substrate binding by blocking the LxxIxE-motif substrate binding pocket on B56α. Relevant to oncogenic activity of CIP2A across human cancers, the N-terminal head domain-mediated interaction with B56α stabilizes CIP2A protein. Functionally, CRISPR/Cas9-mediated single amino acid mutagenesis of the head domain blunted MYC expression and MEK phosphorylation, and abrogated triple-negative breast cancer in vivo tumour growth. Collectively, we discover a unique multi-step hijack and mute protein complex regulation mechanism resulting in tumour suppressor PP2A-B56α inhibition. Further, the results unfold a structural determinant for the oncogenic activity of CIP2A, potentially facilitating therapeutic modulation of CIP2A in cancer and other diseases.
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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.