Affinage

PHLPP2

PH domain leucine-rich repeat-containing protein phosphatase 2 · UniProt Q6ZVD8

Length
1323 aa
Mass
146.8 kDa
Annotated
2026-06-10
83 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PHLPP2 is a negative regulator of the PI3K/Akt pro-survival pathway, originally defined as a phosphatase that dephosphorylates the Akt hydrophobic motif (Ser473), preferentially acting on Akt3 to control downstream effectors such as p27 and thereby restraining cell survival and cell-cycle progression (PMID:17386267). Substrate specificity is conferred by scaffolds that assemble PHLPP2 with its targets: β-arrestin 1 brings PHLPP2 and Akt1 together (PMID:23184957), FKBP51 nucleates a PHLPP2–Akt trimeric complex driving Akt dephosphorylation and neuronal death in ischemia/reperfusion (PMID:24746496), and ENH organizes a PHLPP2–AKT1 complex that dephosphorylates AKT1 and eNOS in endothelium (PMID:32268790). Beyond Akt, PHLPP2 acts on a broader set of signaling proteins—it dephosphorylates AMPK through its PH domain to govern metabolic stress responses (PMID:34608126), dephosphorylates MST1 to release pro-apoptotic JNK/Bim signaling (PMID:29626488), dephosphorylates MYC at Thr58 to stabilize it (PMID:31092557), and binds GRK5 to limit cardiac hypertrophic gene expression (PMID:29628444); it also suppresses NF-κB by competing with MALT1 for Bcl10 binding (PMID:24553260) and promotes BECN1-dependent autophagy (PMID:32116109). A 2025 biochemical and phylogenetic study redefined PHLPP2 as a pseudophosphatase that lost catalytic activity in the metazoan ancestor, retaining only a single zinc ion and no detectable in vitro phosphatase activity, indicating its functions rest on substrate binding and membrane scaffolding rather than direct catalysis (PMID:40168118). PHLPP2 abundance is the principal control point of its activity: it is destabilized by numerous E3 ubiquitin ligases (TRIM46, TRIM22, MARCH1, KCTD17/Cul3, RNF149, FBXO32) downstream of signals including glucagon/PKA phosphorylation and IKKβ phosphorylation (PMID:28859855, PMID:35354796, PMID:38199981, PMID:37658961, PMID:35122633, PMID:41000374), degraded via the lysosome through ATP6V0D2/V-ATPase activity (PMID:41312388), and stabilized by free Raptor antagonizing β-TrCP-mediated degradation (PMID:26743335) and by Hsp90 (PMID:29930380); its expression is transcriptionally repressed by mutant p53 and SNAI2 (PMID:35414774, PMID:35654777) and post-transcriptionally suppressed by multiple oncomiRs targeting its 3'-UTR (PMID:25977341, PMID:26868909, PMID:31715176, PMID:35176309). Through these mechanisms PHLPP2 functions as a context-dependent tumor and metabolic regulator, suppressing Akt-driven growth and lipogenesis in liver and adipose tissue (PMID:26743335, PMID:28859855, PMID:33758172) yet acting as a pro-tumorigenic MYC stabilizer in PTEN-mutant prostate cancer (PMID:31092557).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2007 High

    Established PHLPP2 as an isoform-selective Akt phosphatase, answering how the hydrophobic-motif phosphorylation of Akt is reversed and assigning PHLPP2 to Akt3-specific control of survival/cell-cycle outputs.

    Evidence siRNA knockdown with isoform-specific substrate readouts (p27, HDM2, GSK-3α) in cells

    PMID:17386267

    Open questions at the time
    • Did not resolve how PHLPP2 is recruited to specific Akt isoforms
    • In-cell dephosphorylation does not prove direct catalysis
  2. 2009 High

    A natural L1016S variant linked PHLPP2 phosphatase-domain integrity to Akt/PKC suppression and tumor biology, reinforcing a catalytic model of PHLPP2 function.

    Evidence In vitro phosphatase assays with polymorphic variants plus siRNA depletion in breast cancer cells and tumor/normal pairs

    PMID:19324870

    Open questions at the time
    • A single-residue activity change is consistent with but does not formally prove direct catalysis
    • Mechanism of allele retention in tumors not established
  3. 2009 Medium

    Showed PHLPP2 activity is acutely controlled by upstream regulators (AC6) in cardiomyocytes, introducing the idea that PHLPP2 is gated by physical partners rather than constitutively active.

    Evidence Co-IP, phosphatase activity assays, and AC6 cytoplasmic-domain mutants in primary cardiomyocytes

    PMID:19450723

    Open questions at the time
    • cAMP-independent activation mechanism left undefined
    • Single lab, single tissue context
  4. 2010 Medium

    Demonstrated negative feedback from PI3K/Akt onto PHLPP2 activity, positioning PHLPP2 within a self-limiting insulin-signaling loop.

    Evidence Ex vivo retinal phosphatase activity assays with PI3K inhibitor (LY294002) and insulin stimulation

    PMID:20089132

    Open questions at the time
    • Molecular mediator of PI3K-dependent inhibition not identified
    • Tissue-specific ex vivo result
  5. 2012 High

    Identified β-arrestin 1 as a scaffold conferring Akt1-isoform specificity, explaining how PHLPP2 substrate choice is spatially dictated.

    Evidence Reciprocal siRNA knockdowns (DGKδ, PKCα, PHLPP2, PHLPP1) and co-IP of β-arrestin 1 with PHLPP2/Akt1

    PMID:23184957

    Open questions at the time
    • Structural basis of scaffolding not resolved
    • Generality beyond DGKδ-deficient context untested
  6. 2014 Medium

    Extended PHLPP2 function beyond Akt by showing it suppresses NF-κB through competing with MALT1 for Bcl10 binding, defining a catalysis-independent scaffolding role.

    Evidence Co-IP with IKKβ and Bcl10, competitive displacement, and NF-κB reporter assays

    PMID:24553260

    Open questions at the time
    • Whether IKKβ dephosphorylation is direct vs. via Bcl10-MALT1 blockade unclear
    • Single lab
  7. 2014 Medium

    Defined a FKBP51–PHLPP2–Akt trimeric complex as a driver of neuronal death, showing PHLPP2 acts within multiprotein assemblies in vivo.

    Evidence In vivo co-IP in rat ischemia/reperfusion, antisense PHLPP2 knockdown, p-AKT/caspase-3/histology readouts

    PMID:24746496

    Open questions at the time
    • Direct vs. indirect interactions within the complex not dissected
    • Single in vivo model
  8. 2015 Medium

    Revealed a MYC–PHLPP2 transcriptional axis that suppresses Akt, establishing context-dependent control of PHLPP2 expression in prostate cancer.

    Evidence RapidCaP mouse model with Phlpp2 loss and IL6/STAT3/MYC pathway dissection

    PMID:25829425

    Open questions at the time
    • Direct MYC binding at the PHLPP2 promoter not shown here
    • Single lab
  9. 2015 Medium

    Showed oncomiR (miR-205) and Hsp90/p27 control of PHLPP2 protein/translation, opening the layer of post-transcriptional and stability regulation that governs PHLPP2 abundance.

    Evidence 3'-UTR luciferase reporters, Hsp90-PHLPP2 co-IP, autophagy/invasion and TNFα transcription assays in carcinogenesis models

    PMID:25977341 PMID:29930380

    Open questions at the time
    • Relative contribution of each layer to net PHLPP2 levels unquantified
    • Mechanism connecting PHLPP2 to MMP2 autophagic degradation indirect
  10. 2016 High

    Defined the Raptor–β-TrCP stability axis and oncomiR cluster regulation, establishing proteasomal turnover and miRNA suppression as dominant determinants of PHLPP2-controlled Akt activity and hepatic lipogenesis.

    Evidence Raptor/β-TrCP interaction and stability assays with liver mouse models; miR-17-92/C/EBPβ ChIP and phosphatase activity assays in AML

    PMID:26743335 PMID:26868909

    Open questions at the time
    • How free Raptor competes with β-TrCP mechanistically not fully resolved
    • Cross-tissue generality of the stability axis untested
  11. 2017 High

    Identified glucagon/PKA-driven phosphorylation (Ser1119/Ser1210) coupling PHLPP2 to KCTD17/Cul3 degradation, linking hormonal signaling to PHLPP2 turnover and hepatic steatosis.

    Evidence Mass spectrometry phospho-site/interactor mapping, KCTD17 co-IP, CRISPR-KO hepatoma and liver-specific KO mice

    PMID:28859855

    Open questions at the time
    • Whether phospho-degron creation is the sole trigger unclear
    • Other kinases feeding this degron not enumerated
  12. 2018 Medium

    Expanded the PHLPP2 substrate/partner repertoire to GRK5 and MST1, connecting PHLPP2 to cardiac hypertrophy control and pro-apoptotic Hippo-axis signaling.

    Evidence Co-IP, phosphatase-dead mutant controls and epistasis (GRK5); PHLPP2-MST1 co-IP and knockdown rescue (MST1) in cellular models

    PMID:29626488 PMID:29628444

    Open questions at the time
    • Direct dephosphorylation of GRK5 vs. indirect effect not isolated
    • Single-lab biochemistry
  13. 2019 High

    Established PHLPP2 as a MYC-T58 dephosphorylating MYC stabilizer and a druggable dependency in PTEN-mutant cancer, revealing a pro-tumorigenic role opposite to its Akt-suppressive function.

    Evidence RapidCaP Phlpp2 knockout, MYC phospho-T58 assays, small-molecule PHLPP2 inhibitor cell-killing

    PMID:31092557

    Open questions at the time
    • Reconciliation of Akt-suppressive vs. MYC-stabilizing roles incomplete
    • Inhibitor target specificity not exhaustively defined
  14. 2019 Medium

    Demonstrated PHLPP2 promotion of BECN1-dependent autophagy and additional oncomiR (miR-130a-3p) control, broadening its tumor-suppressive and metabolic outputs.

    Evidence Autophagy flux/CUL4A-BECN1 studies with xenografts; miR-130a-3p KO/overexpression mice, 3'-UTR reporters and AKT-AS160-GLUT4 readouts

    PMID:31715176 PMID:32116109

    Open questions at the time
    • Mechanism by which PHLPP2 blocks CUL4A-mediated BECN1 degradation indirect
    • Single-lab models
  15. 2020 High

    Defined AMPK as a PH-domain-dependent PHLPP2 target and ENH as a vascular scaffold, integrating PHLPP2 into metabolic-stress survival and endothelial NO signaling.

    Evidence Co-IP and PH-domain deletion with glucose-limitation survival assays (AMPK); ENH-AKT1-PHLPP2 co-IP with endothelium-specific knockouts and neointima model (ENH)

    PMID:32268790 PMID:34608126

    Open questions at the time
    • Direct AMPK dephosphorylation vs. complex-mediated effect not fully separated
    • Tissue-restricted scaffolding contexts
  16. 2021 High

    Showed adipocyte PHLPP2 governs systemic lipid handling and that m6A methylation (METTL3) controls PHLPP2 levels, embedding PHLPP2 in inter-organ metabolic crosstalk and developmental signaling.

    Evidence Adipocyte-specific PHLPP2 knockout mice with lipolysis/adiponectin/hepatic FAO readouts; mettl3 knockout zebrafish/endothelial cells with AKT rescue

    PMID:33758172 PMID:33788967

    Open questions at the time
    • Direct m6A site on PHLPP2 transcript not mapped in detail
    • Cross-species generality of vascular phenotype untested
  17. 2022 High

    Mapped a network of E3 ligases (TRIM46, TRIM22) and transcriptional repressors (mutant p53, SNAI2) plus circRNA/miRNA sponging that converge on PHLPP2 abundance to dictate Akt activation, glycolysis, senescence, and chemoresistance.

    Evidence RING-mutant ubiquitination assays, domain-mapping co-IP, ChIP for promoter binding, circANAPC7/miR-373 RNA interaction assays with in vivo tumor models

    PMID:35176309 PMID:35354796 PMID:35414774 PMID:35654777 PMID:38199981

    Open questions at the time
    • Hierarchy and dominance among the many regulators in a given tissue unclear
    • Whether transcriptional and degradative controls act redundantly or sequentially unknown
  18. 2023 Medium

    Added RNF149 and viral V-protein-driven degradation of PHLPP2, showing diverse pathologic stimuli converge on PHLPP2 destabilization to activate PI3K/AKT.

    Evidence Co-IP and E3-ligase-dependent ubiquitination (RNF149) with cisplatin-resistance assays; NDV V-protein co-IP, IF, and MG132 rescue with apoptosis readouts

    PMID:37658961 PMID:38128444

    Open questions at the time
    • Ubiquitination site specificity not mapped
    • Single-lab, model-restricted findings
  19. 2024 Medium

    Added MARCH1 as a further E3 ligase degrading PHLPP2 in oral cancer, consolidating ubiquitin-mediated turnover as a recurrent oncogenic mechanism.

    Evidence Co-IP, ubiquitination assay, MARCH1 knockdown/overexpression with xenograft

    PMID:35122633

    Open questions at the time
    • Degradation site and linkage type not defined
    • Single lab
  20. 2025 High

    Reframed PHLPP2 as a catalytically dead pseudophosphatase, fundamentally challenging the long-standing direct-phosphatase model and implying its functions arise from substrate binding and membrane scaffolding; concurrently mapped FBXO32 and lysosomal (ATP6V0D2/V-ATPase) routes of PHLPP2 destruction.

    Evidence In vitro phosphatase assays with zinc characterization and phylogenomic coevolution analyses (pseudophosphatase); proteomics/co-IP with site-specific K592/K942 ubiquitination (FBXO32) and bafilomycin A1 rescue (ATP6V0D2)

    PMID:40168118 PMID:41000374 PMID:41312388

    Open questions at the time
    • The retained substrate-binding/scaffolding partners under physiological conditions not directly demonstrated
    • Reconciliation of pseudophosphatase model with prior cell-based dephosphorylation data unresolved
    • Whether any residual or conditional catalysis exists in vivo unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a catalytically inactive PHLPP2 produces the dephosphorylation events attributed to it across so many substrates—and which scaffold/adaptor interactions reconstitute that function biochemically—remains the central open question.
  • No reconstituted system reconciles pseudophosphatase status with observed substrate dephosphorylation
  • Direct vs. recruited-catalyst mechanism for each substrate undefined
  • No structural model of PHLPP2 bound to a substrate on membranes

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005829 cytosol 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-1643685 Disease 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-162582 Signal Transduction 3 R-HSA-9612973 Autophagy 1
Partners
AC6AKT1AMPKBCL10GRK5IKKBMST1RAPTOR
Complex memberships
ENH–AKT1–PHLPP2 complexFKBP51–PHLPP2–AKT complexβ-arrestin 1–PHLPP2–Akt1 complex

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 PHLPP2 dephosphorylates the hydrophobic motif (Ser-473) of Akt, thereby inactivating it; PHLPP2 specifically regulates Akt3, modulating phosphorylation of p27, while PHLPP1 regulates Akt2; knockdown of PHLPP2 increases agonist-evoked Akt phosphorylation by nearly two orders of magnitude and inhibits apoptosis/cell-cycle progression. siRNA knockdown, in-cell phosphorylation assays, isoform-specific substrate readouts (p27, HDM2, GSK-3α) Molecular Cell High 17386267
2009 A naturally occurring L1016S polymorphism in the phosphatase domain of PHLPP2 reduces its catalytic activity toward both Akt and PKC in vitro and in cells, resulting in elevated Akt phosphorylation and reduced apoptosis; depletion of the Ser-1016 variant in breast cancer cells confirmed reduced function toward Akt and PKC. In vitro phosphatase assay with polymorphic variants, siRNA depletion of endogenous PHLPP2 variants in breast cancer cells, pair-matched tumor/normal samples The Journal of Biological Chemistry High 19324870
2009 In neonatal rat cardiac myocytes, adenylyl cyclase type 6 (AC6) physically associates with PHLPP2 and inhibits its activity under basal conditions, preventing Akt dephosphorylation; however, isoproterenol or forskolin stimulation acutely activates PHLPP2 in a cAMP-independent manner requiring an intact cytoplasmic domain of AC6, leading to rapid Akt dephosphorylation at Ser473. Co-immunoprecipitation, PHLPP2 phosphatase activity assays, AC6 cytoplasmic-domain mutants, isoproterenol/forskolin stimulation in primary cardiomyocytes Biochemical and Biophysical Research Communications Medium 19450723
2010 In the retina, both PHLPP (PHLPP1) and PHLPPL (PHLPP2) phosphatase activities are significantly decreased in the presence of insulin ex vivo, and this inhibition is PI3K-dependent (reversed by LY294002), demonstrating that the IR-activated PI3K/Akt pathway negatively feeds back to regulate PHLPP2 activity. Ex vivo retinal culture phosphatase activity assays, PI3K inhibitor (LY294002) pre-treatment, insulin stimulation Journal of Neurochemistry Medium 20089132
2012 DGKδ deficiency leads to excessive PKCα activity, which promotes PHLPP2-mediated dephosphorylation of Akt; β-arrestin 1 acts as a scaffold bringing PHLPP2 and Akt1 together, conferring specificity for Akt dephosphorylation. Depletion of PHLPP2 (but not PHLPP1) rescues Akt phosphorylation in DGKδ-deficient cells. siRNA knockdown of DGKδ, PKCα, PHLPP2, PHLPP1; co-immunoprecipitation of β-arrestin 1 with PHLPP2 and Akt1; Akt phosphorylation assays The Journal of Biological Chemistry High 23184957
2014 PHLPP2 interacts with IKKβ kinase and decreases IKKβ phosphorylation, thereby suppressing NF-κB activation; mechanistically, PHLPP2 competes with MALT1 for binding to Bcl10, preventing Bcl10-MALT1 complex formation, NEMO ubiquitination, and downstream IKKβ phosphorylation. PHLPP2 loss enhances these interactions and increases NF-κB-dependent transcription. Co-immunoprecipitation of PHLPP2 with IKKβ and Bcl10, competitive displacement assays, NF-κB reporter assays, PHLPP2 knockdown/overexpression Oncotarget Medium 24553260
2014 In a rat cerebral ischemia/reperfusion model, FKBP51, PHLPP2, and AKT assemble into a trimeric signaling complex; I/R injury enhances interactions among these components, leading to Akt dephosphorylation and neuronal death. Antisense oligonucleotide inhibition of PHLPP2 disrupts complex assembly, reverses p-AKT decrease, and reduces caspase-3 cleavage and CA1 neuron loss. Co-immunoprecipitation in vivo rat I/R model, antisense oligonucleotide knockdown of PHLPP2, western blot for p-AKT, caspase-3, histological neuron counts Brain Research Medium 24746496
2015 MYC strongly activates PHLPP2 transcription in primary prostate cells and prostate cancer metastasis; in Pten/Trp53 mutant cells, IL6-driven STAT3 activation induces MYC which upregulates PHLPP2, suppressing AKT. Genetic loss of Phlpp2 in the RapidCaP mouse model is essential for dictating the proliferation driven by MYC-mediated AKT suppression. Genetic mouse models (RapidCaP), Phlpp2 loss-of-function, IL6/STAT3/MYC pathway dissection, cell proliferation assays, tissue analysis Cancer Discovery Medium 25829425
2015 miR-205 induction following B[a]P/B[a]PDE exposure inhibits PHLPP2 protein translation by targeting PHLPP2-3'-UTR; reduced PHLPP2 contributes to lung inflammation and carcinogenesis. PHLPP2 ectopic expression represses inflammatory TNFα transcription, providing an antitumorigenic mechanism. Luciferase reporter assay for 3'-UTR targeting, ectopic PHLPP2 expression in cell transformation models, B[a]P mouse lung cancer model, TNFα transcription assays Clinical Cancer Research Medium 25977341
2015 p27 stabilizes PHLPP2 protein by inhibiting Hsp90 degradation; Hsp90 directly binds PHLPP2 and protects it from degradation. p27 stabilizes Hsp90 by inhibiting calpain1 gene transcription through attenuation of the Jak1/Stat1 cascade. PHLPP2 in turn inhibits bladder cancer invasion by promoting MMP2 degradation via p62-mediated autophagy. Co-immunoprecipitation of Hsp90-PHLPP2, calpain1 transcription assays, Jak1/Stat1 pathway inhibition, autophagy flux assays, invasion assays Oncogene Medium 29930380
2015 Pull-down assay with morin-conjugated beads demonstrated direct binding of morin to PHLPP2 protein; molecular docking revealed morin occupies the active site of PHLPP2, and morin treatment inhibits PHLPP2 activity and its association with Akt1, thereby preventing oxidant-induced Nrf2 suppression via the Akt/GSK3β/Fyn kinase axis. Morin-conjugated bead pull-down assay, molecular docking, PHLPP2 activity assay (ex vivo), Akt/GSK3β/Fyn pathway western blotting Redox Biology Medium 26513344
2016 Free (mTORC1-independent) Raptor stabilizes PHLPP2 protein by reducing β-TrCP-mediated proteasomal degradation of PHLPP2; this leads to suppression of hepatic Akt activity and lipogenesis. Forced PHLPP2 expression in diet-induced obese mice ameliorates hepatic steatosis. Raptor overexpression/knockdown, β-TrCP interaction studies, PHLPP2 protein stability assays, liver-specific mouse models, triglyceride measurements Nature Communications High 26743335
2016 In AML cells, microRNAs from the miR-17-92 cluster (oncomir-1) target PHLPP2 mRNA and suppress PHLPP2 protein expression; ATRA treatment suppresses miR-17-92 expression and increases PHLPP2 protein and phosphatase activity. This regulation is mediated by transcription factor C/EBPβ, which binds the intronic promoter of the miR-17-92 gene to inhibit its transactivation. miRNA overexpression/knockdown, PHLPP2 phosphatase activity assay, chromatin immunoprecipitation (C/EBPβ on miR-17-92 promoter), ATRA treatment, western blotting Cell Death and Differentiation High 26868909
2017 In obese mice, glucagon/PKA-dependent phosphorylation of PHLPP2 at Ser1119 and Ser1210 promotes PHLPP2 binding to KCTD17 (a substrate-adaptor for Cul3-RING ubiquitin ligases), leading to PHLPP2 ubiquitin-mediated proteasomal degradation. Loss of PHLPP2 prolongs insulin action and increases lipogenic gene expression, causing hepatic steatosis. Mass spectrometry identification of PHLPP2 phosphorylation sites and interactors, KCTD17 co-IP/binding assay, KCTD17 shRNA knockdown in primary hepatocytes and obese mice, CRISPR/Cas9 PHLPP2-knockout hepatoma cells, liver-specific PHLPP2-knockout mice Gastroenterology High 28859855
2018 PHLPP2 physically interacts with GRK5 in neonatal rat ventricular myocytes (NRVMs); PHLPP2 overexpression (in a phosphatase-activity-dependent manner) blocks phenylephrine-induced nuclear accumulation of GRK5 and hypertrophic gene re-expression. Knockdown of PHLPP2 potentiates GRK5-dependent hypertrophic growth, and GRK5 is required for the hypertrophic response induced by PHLPP2 knockdown. Co-immunoprecipitation of PHLPP2 and GRK5, siRNA knockdown, PHLPP2 overexpression with phosphatase-dead mutant controls, cell size measurements, fetal gene expression (ANF, BNP), PE stimulation The Journal of Biological Chemistry Medium 29628444
2018 PHLPP2 interacts with and dephosphorylates MST1 (Mst1) in berberine-treated hepatoma cells; elevated PHLPP2 inactivates Akt by dephosphorylating Ser473, which releases Akt-mediated repression of Mst1, leading to heightened Mst1 phosphorylation at Thr183 and downstream JNK/Bim/Bak pro-apoptotic signaling. PHLPP2 and Mst1 form an autoinhibitory triangle with Akt. Co-immunoprecipitation of PHLPP2-Mst1, western blot for Akt(Ser473) and Mst1(Thr183), PHLPP2/Mst1 knockdown, berberine treatment in HepG2 cells Toxicology and Applied Pharmacology Medium 29626488
2019 PHLPP2 dephosphorylates threonine-58 (T58) of MYC, a phosphorylation site linked to MYC degradation; this renders PHLPP2 a limiting positive regulator of MYC stability. In the RapidCaP mouse model, complete loss of Phlpp2 paradoxically blocks tumor growth by destabilizing MYC. Small-molecule PHLPP2 inhibitors suppress MYC and kill PTEN-mutant cells. RapidCaP genetically engineered mouse model, Phlpp2 knockout, MYC phospho-T58 assays, small-molecule PHLPP2 inhibitor treatment, cell viability assays The Journal of Cell Biology High 31092557
2019 PHLPP2 promotes BECN1 (Beclin1) stabilization, thereby promoting BECN1-dependent macroautophagy, which inhibits bladder cancer tumor cell growth. The mechanism involves PHLPP2 indirectly preventing CUL4A-mediated BECN1 protein degradation. PHLPP2 overexpression/knockdown, autophagy flux assays, xenograft tumor growth, CUL4A interaction studies Autophagy Medium 32116109
2019 Hepatic exosome-derived miR-130a-3p directly targets PHLPP2 mRNA and suppresses its expression in adipocytes, thereby activating AKT-AS160-GLUT4 signaling to improve glucose uptake and attenuate glucose intolerance in high-fat diet mice. miR-130a-3p knockout and overexpression mice, hepatic exosome injection, 3T3-L1 cell transfection, luciferase 3'-UTR reporter for PHLPP2, PHLPP2 siRNA, AKT/AS160/GLUT4 western blotting Metabolism Medium 31715176
2020 PHLPP2 dephosphorylates and inactivates AMPK (pAMPK); the PH domain of PHLPP2 is required for its interaction with pAMPK, for dephosphorylating and inactivating AMPK, and for the apoptotic response to glucose limitation in leukemia cells. PHLPP2 silencing prolongs leukemia cell survival under glucose limitation by promoting AMPK-mediated fatty acid oxidation. Co-immunoprecipitation of PHLPP2-AMPK, PH domain deletion mutants, PHLPP2 siRNA knockdown, metabolic stress (glucose limitation), cell survival/apoptosis assays Cell Death & Disease High 34608126
2021 In adipocytes, PHLPP2 dephosphorylates Akt (Ser473); adipocyte-specific PHLPP2 knockout increases HSL phosphorylation, leading to enhanced lipolysis and increased PPARα-dependent adiponectin secretion, which in turn increases hepatic fatty acid oxidation to prevent obesity-induced fatty liver. Adipocyte-specific PHLPP2 knockout mice (A-PHLPP2), high-fat diet feeding, HSL phosphorylation assays, in vitro and in vivo lipolysis assays, adiponectin secretion measurement, hepatic FAO assays Nature Communications High 33758172
2021 mettl3 knockout/knockdown increases PHLPP2 expression and reduces AKT phosphorylation (S473) with decreased mTOR phosphorylation (S2481), demonstrating that m6A RNA methylation by METTL3 regulates PHLPP2 levels to control vascular development via PHLPP2/mTOR-AKT signaling. CRISPR-Cas9 mettl3 knockout zebrafish, morpholino knockdown, constitutively active AKT1 rescue, METTL3 knockdown in human endothelial cells, PHLPP2/AKT/mTOR western blotting FASEB Journal Medium 33788967
2022 TRIM46 acts as an E3 ubiquitin ligase that directly ubiquitinates PHLPP2 and promotes its proteasomal degradation; this requires the RING domain E3 ligase activity of TRIM46. PHLPP2 degradation activates AKT/HK2 signaling, driving glycolysis and chemoresistance in lung adenocarcinoma. PHLPP2 overexpression reverses these effects. TRIM46 wild-type vs. RING-mutant overexpression, ubiquitination assays, PHLPP2 protein level measurement, co-immunoprecipitation, glycolysis assays, PDX mouse model, cisplatin resistance assays Cell Death & Disease High 35354796
2022 circANAPC7 acts as a sponge for miR-373, preventing miR-373-mediated suppression of PHLPP2; PHLPP2 then dephosphorylates AKT, suppresses cyclin D1, and inhibits TGF-β secretion via STAT5. Additionally, PHLPP2 induces dephosphorylation of CREB, forming a CREB-miR-373-PHLPP2 feed-forward loop. Biotinylated miRNA pulldown, RNA immunoprecipitation, luciferase reporter assays, PHLPP2 western blot, AKT phosphorylation, 3D organoids, mouse models Gastroenterology Medium 35176309
2022 TRIM22, whose expression is transcriptionally upregulated by p53 during IR-induced senescence, directly associates (via its SPRY domain) with the C-terminal domain of PHLPP2 at IKKβ-mediated phosphorylation sites; TRIM22-mediated ubiquitination and proteasomal degradation of PHLPP2 activates AKT-p53-p21 signaling, causing cellular senescence in HCC cells. Co-immunoprecipitation (TRIM22 SPRY domain with PHLPP2 C-terminal domain), ubiquitination assay, TRIM22 overexpression/knockdown, p-AKT/p53/p21 western blot, senescence assays (SA-β-gal), IR treatment Cell Death & Disease High 38199981
2022 Mutant p53 (hotspot mutations) directly binds to the PHLPP2 promoter and transcriptionally inhibits PHLPP2 expression, releasing AKT from PHLPP2-mediated suppression; activated AKT then promotes tumor proliferation/metastasis and via 4EBP1/eIF4E enhances PD-L1 translation, facilitating immune escape. Chromatin immunoprecipitation (mutant p53 on PHLPP2 promoter), PHLPP2 expression analysis in mutant p53 colorectal cancer samples, AKT pathway western blotting, PD-L1 expression assays International Journal of Biological Sciences Medium 35414774
2022 SNAI2 binds to the PHLPP2 promoter region (as detected by chromatin immunoprecipitation) and transcriptionally represses PHLPP2, activating the Akt pathway and promoting glioma stem cell proliferation. Chromatin immunoprecipitation, RT-qPCR, SNAI2/PHLPP2 overexpression and knockdown, Akt phosphorylation assays, GSC proliferation/apoptosis assays, nude mouse xenografts Cell Death & Disease Medium 35654777
2023 The E3 ubiquitin ligase RNF149 physically interacts with PHLPP2 and promotes its E3 ligase-dependent proteasomal degradation, activating PI3K/AKT signaling and conferring cisplatin resistance in esophageal squamous cell carcinoma. Co-immunoprecipitation of RNF149-PHLPP2, ubiquitination assay, RNF149 overexpression/knockdown, PHLPP2 protein stability assays, AKT pathway western blotting, cisplatin resistance assays in vitro and in vivo Medical Oncology Medium 37658961
2023 Newcastle disease virus (NDV) V protein directly interacts with PHLPP2 (co-IP and indirect immunofluorescence) and targets PHLPP2 for ubiquitin-proteasome degradation (inhibited by MG132), thereby activating PI3K/AKT signaling, inhibiting cell apoptosis, and promoting viral replication. Co-immunoprecipitation (NDV V protein with PHLPP2), indirect immunofluorescence, MG132 proteasome inhibition, flow cytometry apoptosis assay, caspase-3 activity assay Veterinary Microbiology Medium 38128444
2024 The E3 ubiquitin ligase MARCH1 physically interacts with PHLPP2 (by co-immunoprecipitation) and promotes PHLPP2 ubiquitination and degradation in oral squamous cell carcinoma, thereby activating AKT signaling and promoting tumor cell proliferation and suppressing apoptosis. Co-immunoprecipitation, ubiquitination assay, MARCH1 knockdown/overexpression, PHLPP2 protein levels, in vivo xenograft Clinical & Translational Oncology Medium 35122633
2025 PHLPP2 is a pseudophosphatase that lost catalytic activity in the metazoan ancestor; it contains a single zinc ion in its catalytic center and has no detectable phosphatase activity in vitro. Despite loss of catalytic activity, surface conservation suggests PHLPP2 may have retained substrate-binding capacity and likely functions as a scaffold on membranes, as supported by phylogenomic coevolution analyses. In vitro phosphatase activity assays, metalloprotein analysis (zinc binding), crystal/structural analysis implied, phylogenetic and phylogenomic analyses, cancer genomics analysis Proceedings of the National Academy of Sciences of the United States of America High 40168118
2025 FBXO32 (F-box protein) interacts with PHLPP2 and promotes K48-linked polyubiquitination of PHLPP2 at K592 and K942 sites, leading to PHLPP2 proteasomal degradation and activation of the PI3K-AKT pathway in hepatocellular carcinoma. Proteomics-based interactome, co-immunoprecipitation, ubiquitination assays identifying K48-linked polyubiquitination at K592/K942, FBXO32 overexpression/knockdown, orthotopic HCC mouse model, HCC patient-derived organoids MedComm Medium 41000374
2025 ATP6V0D2 enhances lysosomal function to promote lysosomal degradation of PHLPP2, thereby sustaining AKT phosphorylation in triple-negative breast cancer; pharmacological inhibition of V-ATPase with bafilomycin A1 blocks PHLPP2 lysosomal degradation, restores PHLPP2 levels, and sensitizes TNBC cells to cisplatin. ATP6V0D2 knockdown, bafilomycin A1 (V-ATPase inhibitor) treatment, PHLPP2 protein stability assays, AKT phosphorylation western blot, in vitro and in vivo cisplatin sensitivity assays, patient-derived organoids iScience Medium 41312388
2020 ENH (Enigma Homolog Protein) forms a scaffold complex with AKT1 and PHLPP2 in arterial endothelial cells; this complex facilitates PHLPP2-mediated dephosphorylation of AKT1 and eNOS, reducing nitric oxide production. Endothelium-specific knockout of either ENH or PHLPP2 in mice reduces ligation-induced neointima formation. Co-immunoprecipitation of ENH-AKT1-PHLPP2 complex, endothelium-specific ENH knockout and PHLPP2 knockout mice, carotid artery ligation model, AKT/eNOS phosphorylation assays, nitric oxide measurement Arteriosclerosis, Thrombosis, and Vascular Biology High 32268790

Source papers

Stage 0 corpus · 83 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms. Molecular cell 493 17386267
2013 miR-205 targets PTEN and PHLPP2 to augment AKT signaling and drive malignant phenotypes in non-small cell lung cancer. Cancer research 181 23856247
2013 microRNA-224 promotes cell proliferation and tumor growth in human colorectal cancer by repressing PHLPP1 and PHLPP2. Clinical cancer research : an official journal of the American Association for Cancer Research 116 23846336
2022 Circular RNA ANAPC7 Inhibits Tumor Growth and Muscle Wasting via PHLPP2-AKT-TGF-β Signaling Axis in Pancreatic Cancer. Gastroenterology 98 35176309
2019 Hepatic exosome-derived miR-130a-3p attenuates glucose intolerance via suppressing PHLPP2 gene in adipocyte. Metabolism: clinical and experimental 80 31715176
2015 MYC Drives Pten/Trp53-Deficient Proliferation and Metastasis due to IL6 Secretion and AKT Suppression via PHLPP2. Cancer discovery 76 25829425
2014 MicroRNA-141 promotes the proliferation of non-small cell lung cancer cells by regulating expression of PHLPP1 and PHLPP2. FEBS letters 64 24945731
2015 Mir-135a enhances cellular proliferation through post-transcriptionally regulating PHLPP2 and FOXO1 in human bladder cancer. Journal of translational medicine 58 25888950
2015 PHLPP2 Downregulation Contributes to Lung Carcinogenesis Following B[a]P/B[a]PDE Exposure. Clinical cancer research : an official journal of the American Association for Cancer Research 58 25977341
2016 mTORC1-independent Raptor prevents hepatic steatosis by stabilizing PHLPP2. Nature communications 56 26743335
2016 MiR-760 overexpression promotes proliferation in ovarian cancer by downregulation of PHLPP2 expression. Gynecologic oncology 54 27726922
2022 TRIM46 activates AKT/HK2 signaling by modifying PHLPP2 ubiquitylation to promote glycolysis and chemoresistance of lung cancer cells. Cell death & disease 53 35354796
2016 MiR-181a Targets PHLPP2 to Augment AKT Signaling and Regulate Proliferation and Apoptosis in Human Keloid Fibroblasts. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 53 27915346
2017 miR-181 elevates Akt signaling by co-targeting PHLPP2 and INPP4B phosphatases in luminal breast cancer. International journal of cancer 50 28224609
2019 MEG3, as a Competing Endogenous RNA, Binds with miR-27a to Promote PHLPP2 Protein Translation and Impairs Bladder Cancer Invasion. Molecular therapy. Nucleic acids 49 30826633
2015 Morin mitigates acetaminophen-induced liver injury by potentiating Nrf2 regulated survival mechanism through molecular intervention in PHLPP2-Akt-Gsk3β axis. Apoptosis : an international journal on programmed cell death 45 26286854
2016 PHLPP2 down regulation influences nuclear Nrf2 stability via Akt-1/Gsk3β/Fyn kinase axis in acetaminophen induced oxidative renal toxicity: Protection accorded by morin. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 42 26767949
2019 The PHLPP2 phosphatase is a druggable driver of prostate cancer progression. The Journal of cell biology 36 31092557
2016 Transcription factor C/EBP-β induces tumor-suppressor phosphatase PHLPP2 through repression of the miR-17-92 cluster in differentiating AML cells. Cell death and differentiation 35 26868909
2015 Suppression in PHLPP2 induction by morin promotes Nrf2-regulated cellular defenses against oxidative injury to primary rat hepatocytes. Redox biology 35 26513344
2009 Common polymorphism in the phosphatase PHLPP2 results in reduced regulation of Akt and protein kinase C. The Journal of biological chemistry 35 19324870
2017 Degradation of PHLPP2 by KCTD17, via a Glucagon-Dependent Pathway, Promotes Hepatic Steatosis. Gastroenterology 34 28859855
2021 Adipocyte PHLPP2 inhibition prevents obesity-induced fatty liver. Nature communications 33 33758172
2018 MiR-135a Protects Vascular Endothelial Cells Against Ventilator-Induced Lung Injury by Inhibiting PHLPP2 to Activate PI3K/Akt Pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 33 30045018
2020 Hyperoside Protected Against Oxidative Stress-Induced Liver Injury via the PHLPP2-AKT-GSK-3β Signaling Pathway In Vivo and In Vitro. Frontiers in pharmacology 31 32765271
2015 miR-372 regulates glioma cell proliferation and invasion by directly targeting PHLPP2. Journal of cellular biochemistry 31 25160587
2024 TRIM22 induces cellular senescence by targeting PHLPP2 in hepatocellular carcinoma. Cell death & disease 30 38199981
2019 LncRNA MBNL1-AS1 represses cell proliferation and enhances cell apoptosis via targeting miR-135a-5p/PHLPP2/FOXO1 axis in bladder cancer. Cancer medicine 30 31769229
2018 PHLPP2 stabilization by p27 mediates its inhibition of bladder cancer invasion by promoting autophagic degradation of MMP2 protein. Oncogene 30 29930380
2014 PHLPP2 suppresses the NF-κB pathway by inactivating IKKβ kinase. Oncotarget 29 24553260
2020 Endothelial Scaffolding Protein ENH (Enigma Homolog Protein) Promotes PHLPP2 (Pleckstrin Homology Domain and Leucine-Rich Repeat Protein Phosphatase 2)-Mediated Dephosphorylation of AKT1 and eNOS (Endothelial NO Synthase) Promoting Vascular Remodeling. Arteriosclerosis, thrombosis, and vascular biology 27 32268790
2022 Mutant p53 achieved Gain-of-Function by promoting tumor growth and immune escape through PHLPP2/AKT/PD-L1 pathway. International journal of biological sciences 24 35414774
2019 Arecoline suppresses epithelial cell viability through the Akt/mTOR signaling pathway via upregulation of PHLPP2. Toxicology 24 30910432
2009 Activation of PH-domain leucine-rich protein phosphatase 2 (PHLPP2) by agonist stimulation in cardiac myocytes expressing adenylyl cyclase type 6. Biochemical and biophysical research communications 24 19450723
2019 PHLPP2 downregulation protects cardiomyocytes against hypoxia-induced injury through reinforcing Nrf2/ARE antioxidant signaling. Chemico-biological interactions 22 31610156
2020 Oncogenic role of MIR516A in human bladder cancer was mediated by its attenuating PHLPP2 expression and BECN1-dependent autophagy. Autophagy 21 32116109
2012 Diacylglycerol kinase δ modulates Akt phosphorylation through pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2). The Journal of biological chemistry 21 23184957
2015 MiR-32 contributed to cell proliferation of human breast cancer cells by suppressing of PHLPP2 expression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20 26276160
2021 Role of epigenetic m6 A RNA methylation in vascular development: mettl3 regulates vascular development through PHLPP2/mTOR-AKT signaling. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 19 33788967
2014 Assembly of the FKBP51-PHLPP2-AKT signaling complex in cerebral ischemia/reperfusion injury in rats. Brain research 19 24746496
2017 miR-938 promotes colorectal cancer cell proliferation via targeting tumor suppressor PHLPP2. European journal of pharmacology 18 28433657
2016 Inhibition of PHLPP2/cyclin D1 protein translation contributes to the tumor suppressive effect of NFκB2 (p100). Oncotarget 18 27095572
2010 Serine/threonine kinase akt activation regulates the activity of retinal serine/threonine phosphatases, PHLPP and PHLPPL. Journal of neurochemistry 18 20089132
2021 Circular RNA circ_0001017 Sensitizes Cisplatin-Resistant Gastric Cancer Cells to Chemotherapy by the miR-543/PHLPP2 Axis. Biochemical genetics 17 34313883
2021 Phosphatase PHLPP2 regulates the cellular response to metabolic stress through AMPK. Cell death & disease 17 34608126
2020 miR-15a-5p targets PHLPP2 in gastric cancer cells to modulate platinum resistance and is a suitable serum biomarker for oxaliplatin resistance. Neoplasma 17 32567934
2018 miR-214-Dependent Increase of PHLPP2 Levels Mediates the Impairment of Insulin-Stimulated Akt Activation in Mouse Aortic Endothelial Cells Exposed to Methylglyoxal. International journal of molecular sciences 17 29425121
2018 Berberine induced modulation of PHLPP2-Akt-MST1 kinase signaling is coupled with mitochondrial impairment and hepatoma cell death. Toxicology and applied pharmacology 17 29626488
2018 PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2) regulates G-protein-coupled receptor kinase 5 (GRK5)-induced cardiac hypertrophy in vitro. The Journal of biological chemistry 15 29628444
2020 HAND2-AS1 Works as a ceRNA of miR-3118 to Suppress Proliferation and Migration in Breast Cancer by Upregulating PHLPP2. BioMed research international 14 33015182
2022 MARCH1 silencing suppresses growth of oral squamous cell carcinoma through regulation of PHLPP2. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 13 35122633
2021 CircRNA circ_0006892 regulates miR-24/PHLPP2 axis to mitigate cigarette smoke extract-induced bronchial epithelial cell injury. Biotechnology and applied biochemistry 13 33734482
2021 Colonic Epithelial PHLPP2 Deficiency Promotes Colonic Epithelial Pyroptosis by Activating the NF-κB Signaling Pathway. Oxidative medicine and cellular longevity 13 34394827
2022 Transcription factor SNAI2 exerts pro-tumorigenic effects on glioma stem cells via PHLPP2-mediated Akt pathway. Cell death & disease 12 35654777
2020 miR-141 Promotes Colon Cancer Cell Proliferation by Targeted PHLPP2 Expression Inhibitionn. Cancer management and research 12 33204152
2023 RNF149 confers cisplatin resistance in esophageal squamous cell carcinoma via destabilization of PHLPP2 and activating PI3K/AKT signalling. Medical oncology (Northwood, London, England) 10 37658961
2023 Newcastle disease virus activates the PI3K/AKT signaling pathway by targeting PHLPP2 degradation to delay cell apoptosis and promote viral replication. Veterinary microbiology 10 38128444
2022 Baicalein ameliorates oxidative stress and brain injury after intracerebral hemorrhage by activating the Nrf2/ARE pathway via miR-106a-5p/PHLPP2 axis. The International journal of neuroscience 10 35612366
2020 The Phosphatase PHLPP2 Plays a Key Role in the Regulation of Pancreatic Beta-Cell Survival. International journal of endocrinology 10 32411219
2023 Knockdown of Mmu-circ-0001380 Attenuates Myocardial Ischemia/Reperfusion Injury via Modulating miR-106b-5p/Phlpp2 Axis. Journal of cardiovascular translational research 9 37474690
2021 LncRNA LOC729178 acts as a sponge of miR-144-3p to mitigate cigarette smoke extract-induced inflammatory injury via regulating PHLPP2 in 16HBE cells. Journal of molecular histology 9 33847879
2020 PHLPP2 is regulated by competing endogenous RNA network in pathogenesis of colon cancer. Aging 9 32633726
2019 miR-762 Promotes Malignant Development of Head and Neck Squamous Cell Carcinoma by Targeting PHLPP2 and FOXO4. OncoTargets and therapy 9 31920332
2018 TIS21/BTG2 inhibits breast cancer growth and progression by differential regulation of mTORc1 and mTORc2-AKT1-NFAT1-PHLPP2 signaling axis. Journal of cancer research and clinical oncology 9 29808317
2023 Insights into the role of PHLPP2/Akt/GSK3β/Fyn kinase/Nrf2 trajectory in the reno-protective effect of rosuvastatin against colistin-induced acute kidney injury in rats. The Journal of pharmacy and pharmacology 8 37095069
2016 Photoreceptor Neuroprotection: Regulation of Akt Activation Through Serine/Threonine Phosphatases, PHLPP and PHLPPL. Advances in experimental medicine and biology 8 26427440
2016 miR-3117 regulates hepatocellular carcinoma cell proliferation by targeting PHLPPL. Molecular and cellular biochemistry 8 27822662
2020 PHLPP2 is a novel biomarker and epigenetic target for the treatment of vitamin C in pancreatic cancer. International journal of oncology 7 32319585
2020 MicroRNA-302a promotes neointimal formation following carotid artery injury in mice by targeting PHLPP2 thus increasing Akt signaling. Acta pharmacologica Sinica 7 32694755
2016 Cheliensisin A (Chel A) induces apoptosis in human bladder cancer cells by promoting PHLPP2 protein degradation. Oncotarget 7 27556506
2013 Inhibitory effect of atorvastatin on the cell growth of cardiac myxomas via the PTEN and PHLPP2 phosphatase signaling pathway. Oncology reports 7 23715723
2019 miR-493 Promotes Prostate Cancer Cells Proliferation by Targeting PHLPP2 and Activating Akt Signaling Pathway. Clinical laboratory 6 30868840
2019 A balancing act: PHLPP2 fine tunes AKT activity and MYC stability in prostate cancer. The Journal of cell biology 6 31145683
2020 MiR-493 Induces Cytotoxic Autophagy in Prostate Cancer Cells through Regulation on PHLPP2. Current pharmaceutical biotechnology 5 32188381
2025 MiR-25-3p regulates pulmonary arteriovenous malformation after Glenn procedure in patients with univentricular heart via the PHLPP2-HIF-1α axis. Scientific reports 4 39900983
2025 PHLPP2 is a pseudophosphatase that lost activity in the metazoan ancestor. Proceedings of the National Academy of Sciences of the United States of America 2 40168118
2025 TRIM46 promotes chemoresistance of ovarian cancer via activating PHLPP2/PI3K/AKT pathway. Biochemistry and cell biology = Biochimie et biologie cellulaire 2 41222281
2021 PHLPP2 gene L1016S (rs61733127) and PIK3R1 gene Met326Ile (rs3730089) polymorphisms are associated with the risk of colon and breast cancers. Nucleosides, nucleotides & nucleic acids 1 34193013
2026 Piezo1-PHLPP2-PI3K/AKT axis represents a novel signalling cascade driving EMT and local invasion in colorectal cancer. Pathology, research and practice 0 41775212
2025 Downregulated miR-199a-3p in Preeclamptic Placenta-derived Exosomes from Cord Blood Hinders VEGF-induced Fetal Glomerular Dysplasia Through Inhibiting Akt1(S473) Phosphorylation via Targeting PHLPP2. Stem cell reviews and reports 0 40892184
2025 Hypomethylation-Enhanced F-Box Protein 32 Promotes Hepatocellular Carcinogenesis via Ubiquitin-Mediated PHLPP2 Degradation. MedComm 0 41000374
2025 ATP6V0D2 drives triple-negative breast cancer progression and inhibits cisplatin sensitivity by promoting PHLPP2 lysosomal degradation. iScience 0 41312388
2024 LncRNA CCAT1 knockdown suppresses tongue squamous cell carcinoma progression by inhibiting the ubiquitination of PHLPP2. Molecular and cellular biochemistry 0 38763996

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