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    GENE:

    PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)

    i
    Other names: PPP2R1A, Protein Phosphatase 2 Scaffold Subunit Aalpha, PP2A-Aalpha, PR65A, PP2AA, Serine/Threonine-Protein Phosphatase 2A 65 KDa Regulatory Subunit A Alpha Isoform, Protein Phosphatase 2 (Formerly 2A), Regulatory Subunit A (PR 65), Alpha Isoform , Protein Phosphatase 2A, Regulatory Subunit A, Alpha Isoform, Protein Phosphatase 2A Structural Subunit A, Alpha Isoform, Protein Phosphatase 2, Regulatory Subunit A, Alpha, Protein Phosphatase 2, 65kDa Regulatory Subunit A, Medium Tumor Antigen-Associated 61 KDA Protein, Medium Tumor Antigen-Associated 61 KDa Protein, Testicular Secretory Protein Li 1, PP2A Subunit A Isoform PR65-Alpha, PP2A Subunit A Isoform R1-Alpha, PP2AAALPHA, MRD36
    Associations

    News

    Trials
    17d
    RP-6306 in Patients With Advanced Cancer (clinicaltrials.gov)
    P2, N=28, Completed, Canadian Cancer Trials Group | Active, not recruiting --> Completed
    Trial completion
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
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    TP53 mutation • KRAS mutation • HER-2 amplification • RAS mutation
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    Herceptin (trastuzumab) • gemcitabine • 5-fluorouracil • irinotecan • leucovorin calcium • lunresertib (RP-6306) • camonsertib (RP-3500)
    26d
    Molecular Landscape of Advanced Endometrial Cancer: Exploratory Analyses at Modena Cancer Center (MEMO). (PubMed, Int J Mol Sci)
    Our findings underscore the need for further investigation into the molecular landscape of advanced endometrial cancer, particularly in the context of therapeutic implications. Combinatorial treatment strategies targeting specific molecular alterations, such as KRAS, in combination with other targeted agents or therapeutic approaches, warrant further exploration.
    Journal
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
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    TP53 mutation • KRAS mutation • PIK3CA mutation • PTEN mutation
    1m
    MYTHIC: Study of Lunresertib Alone or in Combination With RP-3500 or Debio 0123 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=464, Recruiting, Debiopharm International SA | Trial completion date: Dec 2026 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Dec 2027
    Trial completion date • Trial primary completion date
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    CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • MUC16 (Mucin 16, Cell Surface Associated) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
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    lunresertib (RP-6306) • Debio 0123 • camonsertib (RP-3500)
    2ms
    Expression characteristics, prognostic value, and immune-related analysis of PPP2R1A in lung adenocarcinoma. (PubMed, Front Immunol)
    PPP2R1A is overexpressed in LUAD and associated with poor prognosis, potentially serving as an oncogene by regulating key signaling pathways and immune microenvironment. Its knockdown suppresses malignant phenotypes, highlighting its potential as both a prognostic biomarker and therapeutic target in LUAD.
    Journal
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    CD4 (CD4 Molecule) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
    3ms
    Phosphatase PP2A promotes RTA dephosphorylation to impair KSHV lytic replication. (PubMed, PLoS Pathog)
    Interestingly, to evade this host antiviral mechanism, KSHV RTA can promote PPP2R1A degradation through ubiquitin-proteasome pathway. Taken together, we identified that the scaffold protein PPP2R1A is a new binding partner of RTA, and the interaction induces RTA dephosphorylation mediated by phosphatase PP2A, impairing KSHV lytic replication, which provide new insights into the development of novel antiviral strategies.
    Journal
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    PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
    3ms
    Discovery of a bifunctional PKMYT1-targeting PROTAC empowered by AI-generation. (PubMed, Nat Commun)
    It also exhibits favorable oral bioavailability, stronger pharmacodynamic effects relative to the PKMYT1 inhibitor alone, and robust antitumor response as a monotherapy in xenograft models. This PROTAC serves as a precise chemical probe to explore PKMYT1 biology and a promising lead for further cancer therapy exploration.
    Journal
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    CCNE1 (Cyclin E1) • CRBN (Cereblon) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
    4ms
    Succinylation of tumor suppressor PPP2R1A K541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling to display oncogene function. (PubMed, Acta Pharm Sin B)
    In conclusion, succinylation of PPP2R1A lysine 541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling through PCK1 S90 phosphorylation to support liver cancer. Our finding provides new insights into the mechanism by which post-translational modifications (PTMs) confer the conversion of tumor suppressor function to oncogene.
    Journal
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    HAT1 (Histone Acetyltransferase 1) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
    5ms
    NCI-2018-01240: Durvalumab and Tremelimumab in Treating Participants With Recurrent or Refractory Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov)
    P2, N=100, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed
    Trial completion • Platinum resistant
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    PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
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    Imfinzi (durvalumab) • Imjudo (tremelimumab-actl)
    6ms
    Elucidating divergent biology in uterine carcinosarcoma. (PubMed, Transl Oncol)
    By elucidating the complex interplay between the epithelial and mesenchymal components, this study enhances our understanding of UCS and informs the development of novel therapeutic strategies targeting both genomic alterations and the TME.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CCNE1 (Cyclin E1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
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    TP53 mutation • PIK3CA mutation • TMB-L
    6ms
    Whole-genome sequencing-based characterization of endometrial serous carcinoma. (PubMed, Gynecol Oncol)
    Although serous ECs are characterized by TP53 mutations and generally high levels of CNAs, genomic features of HR-deficiency are not prominent. Larger prospective studies of the impact of chromosomal instability on outcome in serous EC patients are warranted.
    Journal
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    TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
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    TP53 mutation • PIK3CA mutation
    6ms
    Epigenetics of Endometrial Cancer: The Role of Chromatin Modifications and Medicolegal Implications. (PubMed, Int J Mol Sci)
    From a medicolegal and policy-making perspective, the implications of using epigenetics in cancer care are briefly explored as well. Epigenetics in endometrial cancer is not only a topic of biomedical interest but also a crossroads between science, ethics, law, and public health, requiring integrated approaches and careful regulation.
    Review • Journal
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    TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • MLH1 (MutL homolog 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
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    PIK3CA mutation • ARID1A mutation
    7ms
    A single gene mutation predicts response to immune checkpoint blockade in ovarian clear cell carcinoma. (PubMed, Mol Oncol)
    Furthermore, preclinical studies have shown that PP2A inhibition leads to the generation of neoantigens by disrupting RNA splicing, and PP2A inhibition can remodel the immune microenvironment of tumors to enhance responses to ICB. The finding that loss-of-function PPP2R1A mutations predict benefit from immunotherapy also suggests that pharmacological inhibition of PP2A may act synergistically with ICB therapy.
    Journal • Checkpoint inhibition • IO biomarker
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    CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)