Affinage

PHLPP1

PH domain leucine-rich repeat-containing protein phosphatase 1 · UniProt O60346

Length
1717 aa
Mass
184.7 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PHLPP1 is a PP2C-family Ser/Thr phosphatase that terminates pro-survival and growth signaling by directly dephosphorylating the hydrophobic motif of AGC kinases, beginning with Akt at Ser473 to trigger apoptosis and suppress tumor growth (PMID:15808505). It exhibits isoform selectivity, preferentially inactivating Akt2 and thereby controlling Akt2-specific substrates HDM2 and GSK-3α (PMID:17386267), and extends the same hydrophobic-motif dephosphorylation logic to PKC (via a PH-domain-dependent mechanism) (PMID:18162466) and to S6K1, where its loss derepresses cap-dependent translation, cell size, and the S6K-IRS1 feedback loop (PMID:21986499). Beyond AGC kinases, PHLPP1 dephosphorylates RAF1 at Ser338 to restrain RAF-MEK-ERK signaling and intestinal tumorigenesis (PMID:24530606), dephosphorylates AMPK at Thr172 in an ERK-primed manner (PMID:29499326), activates the pro-apoptotic kinase MST1 (PMID:22340730, PMID:34348155), and dephosphorylates STAT1 Ser727 in the nucleus to restrain innate-immune transcription, an activity that requires a bipartite NLS in its N-terminal extension and protects mice from lethal endotoxin and bacterial challenge (PMID:31408005). PHLPP1 also serves as a quality-control checkpoint during PKC maturation, eliminating aberrantly active, non-autoinhibited PKC species—a mechanism lost through cancer-associated PKC pseudosubstrate mutations (PMID:30904392). Substrate access is dictated by scaffolds that target PHLPP1 to discrete compartments: Scribble and NHERF1 recruit it to the plasma membrane (PMID:21701506, PMID:21804599), it localizes to mitochondria where it limits Akt-driven hexokinase activity and cardioprotection (PMID:20576936, PMID:28179998), and to the lysosomal membrane where it opposes mTORC2 to control chaperone-mediated autophagy (PMID:26118642). PHLPP1 abundance is set by a multilayered control system: SCF(β-TrCP)-mediated degradation requiring sequential CKI/GSK-3β phosphorylation, embedded in a PI3K/Akt feedback loop (PMID:19797085), opposing deubiquitinases USP46, USP1, and USP12/WDR48 (PMID:22391563, PMID:22426999, PMID:24145035), mTOR-dependent translation (PMID:21177869), calpain-dependent proteolysis in neurons (PMID:17382888), and HDAC3-mediated transcriptional repression (PMID:23408427). Through these activities PHLPP1 functions as a tumor suppressor across glioma, colorectal, and prostate cancers, and contributes to physiological control of circadian period consolidation (PMID:20080691), regulatory T-cell function (PMID:21498666), and β-cell survival in diabetes (PMID:34348155).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2005 High

    Established that a dedicated phosphatase, not just kinase withdrawal, terminates Akt signaling by removing the hydrophobic-motif phosphate that defines the active kinase.

    Evidence in vitro phosphatase assay, S473D Akt rescue mutagenesis, glioblastoma reintroduction, and xenograft suppression

    PMID:15808505

    Open questions at the time
    • Did not resolve isoform selectivity among Akt1/2/3
    • Did not define how PHLPP1 is targeted to its substrate in vivo
  2. 2007 High

    Resolved that PHLPP1 is isoform-selective, preferentially terminating Akt2 and its specific downstream substrates, distinguishing it from PHLPP2.

    Evidence reciprocal siRNA knockdown of PHLPP isoforms with Akt2-specific substrate (HDM2, GSK-3α) readouts

    PMID:17386267

    Open questions at the time
    • Structural basis of isoform preference unresolved
    • How selectivity is enforced spatially not addressed
  3. 2007 High

    Extended PHLPP1 substrate scope beyond Akt to PKC and linked its neuronal pool (SCOP) to calpain-controlled MAPK/CREB-dependent memory.

    Evidence PKCβII deletion mutagenesis/dephosphorylation assays and calpain-inhibitor plus transgenic forebrain-overexpression behavioral assays

    PMID:17382888 PMID:18162466

    Open questions at the time
    • PH-domain vs PDZ-motif requirements for distinct substrates only partially mapped
    • Direct neuronal substrate downstream of SCOP not fully defined
  4. 2009 High

    Defined how PHLPP1 abundance is controlled, identifying a phosphodegron-driven SCF(β-TrCP) degradation pathway embedded in an Akt-GSK-3β negative-feedback loop.

    Evidence β-TrCP ΔF-box mutant, ubiquitination assays, and CKI/GSK-3β kinase-inhibitor dependency mapping

    PMID:19797085

    Open questions at the time
    • In vivo relevance of the feedback loop not tested
    • Other degradation inputs not yet integrated
  5. 2010 High

    Identified compartment-specific and physiological roles—mitochondrial Akt control with cardioprotection, mTOR-translational regulation of PHLPP, circadian period consolidation, and a nuclear-capable PHLPP1α splice variant.

    Evidence mitochondrial fractionation plus ischemia/reperfusion in KO mice, mTOR/rapamycin perturbations, circadian phase-shift assays in KO mice, and hippocampal fractionation of PHLPP1α

    PMID:20080691 PMID:20576936 PMID:20819118 PMID:21177869

    Open questions at the time
    • Mechanism of mitochondrial vs nuclear targeting incompletely defined
    • Circadian molecular substrate not pinpointed
  6. 2011 High

    Established scaffold-directed spatial control of PHLPP1 and broadened its tumor-suppressive substrate range to S6K1, while linking it to MST1 activation and Treg biology.

    Evidence reciprocal Scribble and NHERF1 co-IP/localization with growth readouts, S6K1 gain/loss-of-function with translational readouts, KO-mouse Treg suppression assays, and review-summarized MST1 phosphatase data

    PMID:21498666 PMID:21701506 PMID:21804599 PMID:21986499 PMID:22340730

    Open questions at the time
    • Whether scaffolds act combinatorially is unclear
    • MST1 activation mechanism described only via review, not primary detail here
  7. 2011 High

    Showed PHLPP1 stability is positively regulated by deubiquitinases and that mislocalization of β-TrCP can uncouple the degradation feedback loop in cancer.

    Evidence USP46 in vitro deubiquitination and reciprocal knockdown, plus β-TrCP1 nuclear-mislocalization rescue in glioblastoma cells

    PMID:21454620 PMID:22391563

    Open questions at the time
    • Hierarchy among competing DUBs not established
    • Generality of β-TrCP mislocalization across tumor types untested
  8. 2012 Medium

    Added USP1 as a further deubiquitinase stabilizing PHLPP1 in lung cancer, reinforcing DUB-mediated control of PHLPP1 half-life.

    Evidence co-IP, GST pull-down, and cycloheximide-chase with USP1 knockdown

    PMID:22426999

    Open questions at the time
    • Single study without reciprocal in vivo validation
    • Relationship to USP46/USP12 redundancy unresolved
  9. 2013 High

    Identified the USP12/WDR48 complex as a PHLPP1-stabilizing deubiquitinase with a cancer-associated loss-of-function mutation, and revealed transcriptional repression of PHLPP1 by HDAC3.

    Evidence tandem affinity purification and in vitro deubiquitination with the WDR48 L580F mutant, plus HDAC3 ChIP at the PHLPP1 promoter in conditional-KO chondrocytes

    PMID:23408427 PMID:24145035

    Open questions at the time
    • Integration of multiple DUBs into a single regulatory logic unresolved
    • TGFβ/Smad control of PHLPP1 transcription only partially mapped
  10. 2013 Medium

    Demonstrated that PH-domain-targeted small molecules (tocopherols) can drive PHLPP1 to the membrane to enforce Akt Ser473 dephosphorylation, and identified a low-confidence c-Jun-binding/apoptotic role.

    Evidence PH-domain binding-affinity and membrane-recruitment assays with xenografts; separate co-IP with PHLPP1 overexpression and dominant-negative c-Jun rescue

    PMID:23512990 PMID:25281487

    Open questions at the time
    • c-Jun interaction rests on a single low-confidence study lacking reciprocal validation
    • Pharmacological PH-domain targeting not validated genetically
  11. 2014 High

    Expanded PHLPP1 to direct RAF-MEK-ERK control via RAF1 Ser338 dephosphorylation, SRPK1-mediated recruitment to Akt, and STAT1 Ser727-dependent macrophage immunomodulation.

    Evidence in vitro RAF1 dephosphorylation with Apc(Min)/Phlpp1-/- mice, phosphoproteomics plus SRPK1-PHLPP1-Akt co-IP in KO MEFs, and macrophage gain/loss-of-function with kinase-inhibitor dissection

    PMID:24443556 PMID:24530606 PMID:24703948

    Open questions at the time
    • How SRPK1 dosage bidirectionally controls recruitment mechanistically unclear
    • Crosstalk between RAF1 and Akt branches not integrated
  12. 2015 High

    Defined a lysosomal PHLPP1 pool that opposes mTORC2 to govern chaperone-mediated autophagy, and connected PHLPP1 loss to FoxO1/FGF18-driven chondrocyte ERK activity.

    Evidence lysosomal fractionation with CMA translocation-complex assays, and KO-chondrocyte multi-substrate phosphorylation with FGFR-inhibitor rescue

    PMID:25953896 PMID:26118642

    Open questions at the time
    • Mechanism of lysosomal targeting of PHLPP1 unresolved
    • Direct vs indirect FoxO1 regulation not separated
  13. 2017 Medium

    Showed PHLPP1 restrains glycolytic metabolism through a mitochondrial PHLPP-Akt-HK2 complex, linking the phosphatase to cancer metabolic dependency.

    Evidence mitochondrial co-IP of the trimeric complex with Seahorse flux and inhibitor rescue in colon cancer cells

    PMID:28179998

    Open questions at the time
    • Single-lab study without in vivo metabolic validation
    • Whether PHLPP1 dephosphorylates HK2 directly or acts via Akt unresolved
  14. 2018 High

    Established AMPK Thr172 as a direct PHLPP1 substrate and showed ERK1/2 phosphorylation of PHLPP1α Ser932 licenses this interaction under ER stress.

    Evidence endogenous co-IP, in vitro AMPK dephosphorylation, Ser932 phospho-site mutagenesis, and validation in knockdown mice

    PMID:29499326

    Open questions at the time
    • Physiological contexts where AMPK regulation dominates over Akt regulation unclear
    • Structural basis of Ser932-dependent substrate switching unknown
  15. 2019 High

    Defined PHLPP1 as a PKC maturation proofreader and a nuclear STAT1 Ser727 phosphatase, plus FKBP51/lncRNA-PCAT1-regulated scaffolding to Akt and an eIF2α interaction influencing chemoresistance.

    Evidence PKC pseudosubstrate-mutant stability analysis across >5,000 tumors, STAT1 Ser727 dephosphorylation with NLS mutagenesis and in vivo infection models, FKBP51/Akt/PHLPP brain co-IP with neuronal survival assays, RIP/RNA pull-down showing PCAT1-FKBP51, and eIF2α co-IP

    PMID:30734931 PMID:30773595 PMID:30904392 PMID:31408005 PMID:34663797

    Open questions at the time
    • How a single phosphatase coordinates cytoplasmic, mitochondrial, lysosomal and nuclear pools is not integrated
    • eIF2α regulation rests on a single co-IP-based study
  16. 2020 Low

    Reported a contrarian observation that PHLPP overexpression can increase Akt phosphorylation via TRAF6/K63-ubiquitination, challenging the canonical phosphatase model.

    Evidence FKBP51 TPR-mutant and K63-ubiquitination assays with PHLPP silencing/overexpression in melanoma cells

    PMID:36781840

    Open questions at the time
    • Contradicts the prevailing model and awaits independent replication
    • Mechanism by which a phosphatase would stabilize an E3 ligase unexplained
  17. 2021 High

    Showed PHLPP1/2 form an mTORC1-driven regulatory loop controlling β-cell apoptosis through AKT and MST1, with therapeutic relevance in diabetes.

    Evidence genetic inhibition of PHLPP in β-cell lines and primary human T2D islets with AKT/MST1 phosphorylation and apoptosis readouts in vivo

    PMID:34348155

    Open questions at the time
    • Relative contributions of AKT vs MST1 branches to β-cell death not separated
    • Translational targeting strategy not defined
  18. 2022 Medium

    Linked PHLPP1 to macrophage lipid metabolism via an AMPK/ChREBP-dependent program, with conserved roles across zebrafish and C. elegans.

    Evidence PHLPP1 gain/loss-of-function with RNA-Seq, ChREBP co-IP, Fasn ChIP, and CRISPR/ortholog deletion in vivo

    PMID:35141506

    Open questions at the time
    • Whether the lipid phenotype is a direct ChREBP effect or downstream of AMPK dephosphorylation unresolved
    • Single-lab in vivo models

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PHLPP1 integrates its many scaffold-defined subcellular pools and competing degradation/stabilization inputs into substrate selection in a given cell type remains unresolved.
  • No unified structural model of substrate/scaffold recognition
  • Rules governing which substrate dominates in a given compartment are unknown
  • Reconciliation of the contrarian Akt-stabilizing report with the canonical phosphatase model is outstanding

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0016787 hydrolase activity 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 2 GO:0005739 mitochondrion 2 GO:0005829 cytosol 2 GO:0005764 lysosome 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1430728 Metabolism 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-9612973 Autophagy 2 R-HSA-9909396 Circadian clock 1
Partners
AKT2BTRCFKBP51NHERF1SCRIBBLESRPK1USP46WDR48
Complex memberships
FKBP51-Akt-PHLPP complexNHERF1-PHLPP1-PTEN complexPHLPP-Akt-HK2 mitochondrial complexScribble-PHLPP1-Akt complex

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 PHLPP1 (then called PHLPP) directly dephosphorylates Akt at the hydrophobic motif (Ser473 in Akt1), thereby inactivating Akt, triggering apoptosis, and suppressing tumor growth. Cells expressing an S473D Akt construct were resistant to PHLPP-induced apoptosis, confirming the hydrophobic motif is the primary cellular target. In vitro phosphatase assay, mutagenesis (S473D Akt), overexpression/reintroduction in glioblastoma cell line, xenograft tumor suppression assay Molecular cell High 15808505
2007 PHLPP1 specifically dephosphorylates Akt2 (hydrophobic motif), while PHLPP2 preferentially targets Akt3; knockdown studies show that PHLPP1 selectively modulates phosphorylation of Akt2 substrates HDM2 and GSK-3α, revealing isoform-selective termination of Akt signaling. siRNA knockdown of individual PHLPP isoforms, phosphorylation assays of Akt isoform-specific downstream substrates, agonist-evoked Akt phosphorylation measurements Molecular cell High 17386267
2007 PHLPP1 and PHLPP2 dephosphorylate the hydrophobic motif of PKC βII, shunting PKC to the detergent-insoluble fraction and effectively terminating its life cycle; deletion mutagenesis shows the PH domain is necessary for effective dephosphorylation of PKC βII, whereas the PDZ-binding motif (required for Akt regulation) is dispensable. Knockdown of PHLPP reduces the rate of phorbol ester-triggered dephosphorylation of the hydrophobic motif of PKC α. Deletion mutagenesis, overexpression, siRNA knockdown, phorbol ester-triggered dephosphorylation assay, detergent-insoluble fractionation The Journal of biological chemistry High 18162466
2009 PHLPP1 protein stability is regulated by the SCF(β-TrCP) E3 ubiquitin ligase in a phosphorylation-dependent manner: β-TrCP recognizes a phosphodegron on PHLPP1 that requires sequential phosphorylation by casein kinase I and GSK-3β. Activation of the PI3K/Akt pathway suppresses PHLPP1 degradation by inhibiting GSK-3β activity, creating a negative feedback loop. β-TrCP overexpression and ΔF-box mutant, siRNA knockdown, ubiquitination assay, kinase inhibitor studies (GSK-3β, casein kinase I), co-immunoprecipitation Molecular and cellular biology High 19797085
2010 PHLPP1 is expressed in the suprachiasmatic nucleus and oscillates in a circadian fashion. PHLPP1-null mice display normal circadian rhythmicity but have drastically impaired capacity to stabilize the circadian period after light-induced resetting, producing large phase shifts, indicating PHLPP1 controls consolidation of circadian periodicity after resetting. PHLPP1 knockout mice, circadian behavior assay, light-pulse phase-shift experiments Proceedings of the National Academy of Sciences of the United States of America Medium 20080691
2010 PHLPP1 dephosphorylates Akt at Ser473 in cardiomyocytes; PHLPP-1 localizes to mitochondria, and PHLPP-1 knockdown potentiates LIF-mediated increases in mitochondrial pAkt and mitochondrial hexokinase-II. PHLPP1 KO mice show increased Akt phosphorylation during ischemia/reperfusion and significantly reduced infarct size. siRNA knockdown in neonatal rat ventricular myocytes, mitochondria/cytosol fractionation, PHLPP1 knockout mice, isolated perfused heart ischemia/reperfusion model Circulation research High 20576936
2011 PHLPP1 is recruited to the cell membrane by binding the scaffolding protein Scribble; knockdown of Scribble redistributes PHLPP1 from membrane to cytoplasm and increases Akt phosphorylation, whereas Scribble overexpression has the opposite effect. PHLPP1-dependent inhibition of cell proliferation requires formation of a Scribble–PHLPP1–Akt trimeric complex. Co-immunoprecipitation, siRNA knockdown of Scribble, subcellular fractionation/membrane localization assays, overexpression EMBO reports Medium 21701506
2011 PHLPP directly dephosphorylates and activates the pro-apoptotic kinase Mst1, thereby promoting apoptosis, in addition to its role in inactivating Akt, PKC, and S6 kinase via hydrophobic motif dephosphorylation. Phosphatase assay, overexpression, apoptosis assays (referenced in review summarizing prior experimental work) The FEBS journal Medium 22340730
2011 PHLPP1 and PHLPP2 dephosphorylate S6K1 at its hydrophobic motif independently of Akt dephosphorylation; knockdown of PHLPP increases S6K1 phosphorylation, activates the S6K-dependent negative feedback to IRS-1, and increases cap-dependent translation, cell size, and protein content. PHLPP overexpression and siRNA knockdown, S6K1 phosphorylation assay, translation initiation complex pulldown, cell size/protein content measurements Molecular and cellular biology High 21986499
2011 PHLPP1 requires NHERF1 for membrane localization and growth-suppressive effects; NHERF1 interacts with PHLPP1/PHLPP2 via its PDZ domains and scaffolds heterotrimeric complexes with PTEN. PHLPP1 loss boosts Akt phosphorylation only in PTEN-negative cells. Co-immunoprecipitation, subcellular localization assays, PHLPP1/PHLPP2 knockdown, glioma patient sample analysis Oncogene Medium 21804599
2011 PHLPP1 expression is elevated in regulatory T cells (Tregs) compared to conventional T cells; knockdown of PHLPP1 restores TCR-mediated Akt activation in Tregs. PHLPP1 KO mice show reduced suppressive capacity of Tregs and impaired induced Treg development, identifying PHLPP1 as the molecular basis for reduced Akt activity in Tregs. PHLPP1 siRNA knockdown in Tregs, PHLPP1 KO mice, Treg suppression assays, Treg differentiation assays Journal of immunology High 21498666
2011 The deubiquitinase USP46 stabilizes PHLPP1 and PHLPP2 by directly removing polyubiquitin chains from PHLPP in vitro and in cells; knockdown of USP46 decreases PHLPP stability and increases Akt phosphorylation, whereas increased USP46 expression decreases PHLPP ubiquitination. Co-immunoprecipitation, in vitro deubiquitination assay, siRNA knockdown of USP46, ubiquitination assay in cells Oncogene High 22391563
2011 The beta-TrCP1 E3 ligase is mislocalized to the nucleus in glioblastoma cells (versus cytoplasmic in normal brain/astrocytoma), spatially separating it from cytoplasmic PHLPP1 and uncoupling the negative feedback loop whereby active Akt promotes PHLPP1 degradation. Restoring cytosolic β-TrCP1 localization rescues Akt-dependent regulation of PHLPP1 stability. Subcellular fractionation, immunofluorescence localization, β-TrCP1 re-localization rescue experiment, pharmacological and overexpression studies in glioblastoma vs. astrocytoma cell lines The Journal of biological chemistry Medium 21454620
2012 USP1 deubiquitinase stabilizes PHLPP1 by interacting with it (demonstrated by co-immunoprecipitation and GST pull-down); silencing USP1 decreases PHLPP1 half-life and increases Akt phosphorylation in lung cancer cells. Co-immunoprecipitation, GST pull-down, cycloheximide chase assay, siRNA knockdown of USP1 Journal of cancer research and clinical oncology Medium 22426999
2013 WDR48 in complex with the deubiquitinase USP12 deubiquitinates PHLPP1, enhancing its protein stability; both WDR48 and USP12 negatively regulate Akt activation. A cancer-associated somatic mutation in WDR48 (L580F) is defective in stabilizing PHLPP1. Tandem affinity purification, co-immunoprecipitation, in vitro deubiquitination assay, overexpression and knockdown, cancer mutation analysis The Journal of biological chemistry High 24145035
2013 HDAC3 represses PHLPP1 expression by associating with the PHLPP1 promoter at Smad binding elements; conditional deletion of HDAC3 in chondrocytes increases PHLPP1 expression and reduces Akt phosphorylation. TGFβ stimulation releases HDAC3 from the Phlpp1 promoter. Chromatin immunoprecipitation (ChIP), HDAC3 conditional knockout chondrocytes, HDAC inhibitor treatment, constitutively active Akt rescue The Journal of biological chemistry Medium 23408427
2013 PHLPP1 interacts with and binds c-Jun protein, and ectopic PHLPP1 expression blocks c-Jun activation and the associated p53 induction and apoptosis. Treatment with Cheliensisin A promotes PHLPP1 protein degradation, releasing c-Jun from PHLPP1-mediated inhibition and allowing c-Jun phosphorylation. Co-immunoprecipitation, overexpression of PHLPP1, dominant-negative c-Jun (TAM67) rescue, assessment of c-Jun phosphorylation and apoptosis Cancer prevention research Low 25281487
2013 Vitamin E (α- and γ-tocopherol) facilitates site-specific dephosphorylation of Akt Ser473 by promoting PH domain-dependent recruitment of both Akt and PHLPP1 to the plasma membrane; binding affinities for the PH domains of Akt and PHLPP1 were greater than for other PH domain-containing proteins. Membrane recruitment assay, PH domain binding affinity measurement, molecular modeling, structural optimization of tocopherols, xenograft tumor models Science signaling Medium 23512990
2014 PHLPP1 and PHLPP2 dephosphorylate RAF1 at Ser338, inhibiting its kinase activity in vitro and in colorectal cancer cells. Knockdown of PHLPP1 or PHLPP2 increases the amplitude and duration of RAF-MEK-ERK signaling and promotes epithelial-mesenchymal transition; Apc(Min)/Phlpp1(-/-) mice develop larger and more invasive intestinal tumors. Co-immunoprecipitation, in vitro dephosphorylation assay of RAF1, siRNA/shRNA knockdown and overexpression, Apc(Min)/Phlpp1(-/-) mouse model, migration/invasion assays Gastroenterology High 24530606
2014 SRPK1 promotes recruitment of PHLPP1 to Akt; downregulation of SRPK1 impairs PHLPP1 recruitment to Akt resulting in constitutive Akt activation, while SRPK1 overexpression sequesters/squelches PHLPP1 away from Akt, also constitutively activating Akt. Both directions of SRPK1 dysregulation thus impair PHLPP1-mediated Akt dephosphorylation. Genome-wide phosphoproteomics, co-immunoprecipitation of SRPK1-PHLPP1-Akt, SRPK1 knockout mouse embryonic fibroblasts, cell transformation assays Molecular cell High 24703948
2015 PHLPP1 associates with the lysosomal membrane and counteracts the inhibitory effect of mTORC2 on chaperone-mediated autophagy (CMA). Lysosomal Akt, a target of the mTORC2/PHLPP1 kinase-phosphatase pair, modulates CMA activity by controlling the dynamics of assembly and disassembly of the CMA translocation complex at the lysosomal membrane. Lysosomal membrane fractionation, co-immunoprecipitation, CMA activity assays, PHLPP1 knockdown/overexpression, translocation complex assembly assays Molecular cell High 26118642
2015 Phlpp1 deficiency in chondrocytes enhances phosphorylation of Akt2, PKC, and p70 S6 kinase. Phlpp1 loss diminishes FoxO1 levels leading to increased Fgf18 expression, elevated MEK/ERK activity, and increased chondrocyte metabolic activity. Chemical inhibition of Fgfr-signaling abrogates the elevated ERK1/2 phosphorylation in Phlpp1-null cultures. Phlpp1 knockout mice, ex vivo chondrocyte cultures, phosphorylation assays for multiple substrates, Phlpp inhibitor treatment, FGFR inhibitor rescue The Journal of biological chemistry Medium 25953896
2018 Endogenous PHLPP1 (but not PP2Cα) directly interacts with and dephosphorylates AMPK at Thr172 in myoblasts without affecting its upstream kinase LKB1. ERK1/2 phosphorylates PHLPP1α at Ser932 under ER stress, and this phosphorylation is required for PHLPP1's ability to interact with and dephosphorylate AMPK. Co-immunoprecipitation of endogenous proteins, in vitro dephosphorylation assay of AMPK, PHLPP1 knockdown mice, ERK1/2 kinase assay, phospho-site mutagenesis of PHLPP1 Ser932 Biochimica et biophysica acta. Molecular basis of disease High 29499326
2019 PHLPP1 provides a proofreading/quality control step during PKC maturation: it opposes PKC phosphorylation at the hydrophobic motif during biosynthesis, targeting aberrantly active species that fail to become autoinhibited for degradation. Cancer-associated hotspot mutations in the PKCβ pseudosubstrate that impair autoinhibition result in dephosphorylated and unstable enzymes, revealing this as a cancer loss-of-function mechanism. Protein-level analysis across >5,000 patient tumors, overexpression of pseudosubstrate mutants, PKC phosphorylation and stability assays, PHLPP1 manipulation Molecular cell High 30904392
2019 PHLPP1 dephosphorylates the transcription factor STAT1 on Ser727 to inhibit its activity, reduce its promoter residency, and reduce expression of target genes involved in innate immunity and cytokine signaling. This function requires a bipartite nuclear localization signal in PHLPP1's unique N-terminal extension. PHLPP1 deletion protects mice from lethal LPS challenge and E. coli infection. PHLPP1 knockout mice, LPS/E. coli infection models, STAT1 phosphorylation assays, chromatin immunoprecipitation (STAT1 promoter occupancy), mutagenesis of nuclear localization signal, macrophage gene expression analysis eLife High 31408005
2019 FKBP51 forms a complex with Akt and PHLPP; this interaction is increased in the absence of Pink1. Overexpression of FKBP51 negatively regulates Akt phosphorylation at Ser473, and knockdown of PHLPP in Pink1 KO neurons rescues neuronal death in response to MPP+, suggesting FKBP51 scaffolds PHLPP1 to Akt to promote dephosphorylation. Co-immunoprecipitation of endogenous FKBP51/Akt/PHLPP from MEFs and brain tissue, shRNA knockdown of PHLPP, adeno-associated virus FKBP51 overexpression in cortical neurons, MPP+ neurotoxin assay Journal of neurochemistry Medium 30734931
2019 lncRNA PCAT1 binds directly to FKBP51 and displaces PHLPP from the PHLPP/FKBP51/IKKα complex, leading to activation of AKT and NF-κB signaling. Targeting PCAT1 restores PHLPP binding to FKBP51 and suppresses AKT signaling. RIP (RNA immunoprecipitation), RNA pull-down, co-immunoprecipitation of PHLPP/FKBP51/IKKα complex, preclinical mouse model of CRPC Nucleic acids research Medium 30773595
2010 PHLPP1 splice variant PHLPP1α (but not PHLPP1β/SCOP) inhibits AKT in hippocampal neurons; PHLPP1α can be localized to the nucleus whereas other PHLPP proteins are found only in the cytosolic fraction. PHLPP1α expression increases dramatically in the hippocampus during development. Subcellular fractionation of hippocampal neurons, direct verification of AKT inhibition by PHLPP1α overexpression, developmental expression analysis Journal of neurochemistry Medium 20819118
2014 A novel immunomodulatory function of PHLPP1 in macrophages: PHLPP1 suppresses LPS/IFN-γ-induced iNOS expression by dephosphorylating STAT1 Ser727. PHLPP1 reduces IFN-γ-stimulated ERK1/2 phosphorylation (contributing to STAT1 Ser727 inhibition) and suppresses LPS-induced p38-dependent IFN-β feedback that drives STAT1 Tyr701 phosphorylation. PHLPP1 overexpression and siRNA/shRNA knockdown in RAW264.7 macrophages, iNOS promoter reporter assay, STAT1 phosphorylation analysis, ERK1/2 and p38 inhibitor studies Journal of leukocyte biology Medium 24443556
2019 PHLPP1 interacts with eIF2α (demonstrated by co-immunoprecipitation) and knockdown of PHLPP1 increases eIF2α phosphorylation and expression of downstream autophagy-associated genes (eIF2α/ATF4 axis), promoting chemoresistance in colon cancer cells under ER stress. Co-immunoprecipitation, siRNA knockdown, overexpression of degradation-resistant PHLPP1 mutant, eIF2α phosphorylation assay Cell death & disease Medium 34663797
2021 PHLPP1/2 are upregulated by sustained mTORC1 hyper-activation in diabetic β-cells; PHLPPs directly dephosphorylate and regulate the activities of β-cell survival kinases AKT and MST1, constituting a regulatory triangle loop controlling β-cell apoptosis. Genetic inhibition of PHLPPs markedly improves β-cell survival in experimental diabetes models and primary human T2D islets. Genetic inhibition (siRNA/KO) of PHLPP in β-cell lines and primary human islets, mTORC1 manipulation, AKT and MST1 phosphorylation assays, β-cell apoptosis/function assays in vivo and in vitro Cell reports High 34348155
2022 PHLPP1 promotes neutral lipid accumulation in macrophages through AMPK/ChREBP-dependent lipid uptake and fatty acid synthesis pathways; PHLPP1 interacts with and modestly increases ChREBP recruitment to the Fasn promoter. Pharmacological inhibition or CRISPR/Cas9-mediated disruption of PHLPP1 reduces lipid accumulation in high-fat-diet-fed zebrafish. PHLPP1 overexpression and knockdown in macrophages, RNA-Seq, co-immunoprecipitation of PHLPP1-ChREBP, Fasn promoter ChIP, CRISPR/Cas9 knockout in zebrafish, C. elegans ortholog (phlp-2) deletion iScience Medium 35141506
2007 Proteolytic degradation of SCOP (PHLPP1) by calpain in hippocampal neurons is triggered by BDNF, KCl depolarization, or NMDA stimulation. SCOP negatively regulates ERK1/2 MAP kinase and CREB-mediated transcription; its degradation contributes to MAPK activation during memory formation. Transgenic mice overexpressing SCOP in the forebrain were completely blocked for novel object memory. Calpain inhibitor experiments, Western blot for SCOP in hippocampus after stimulation and after novel object training, transgenic mouse overexpression of SCOP (inducible forebrain), novel object memory assay Cell High 17382888
2017 PHLPP forms a complex with Akt and hexokinase 2 (HK2) in the mitochondrial fraction of colon cancer cells; knockdown of PHLPP enhances Akt-mediated phosphorylation and mitochondrial localization of HK2, increasing glycolytic flux and causing glucose addiction in colon cancer cells. Co-immunoprecipitation of PHLPP-Akt-HK2 complex from mitochondrial fraction, siRNA knockdown, Seahorse extracellular flux assay, Akt and HK2 inhibitor rescue Cell death discovery Medium 28179998
2010 PHLPP expression is controlled by mTOR-dependent protein translation: rapamycin treatment or mTOR knockdown decreases PHLPP protein expression; knockdown of TSC2 increases PHLPP expression; rapamycin-mediated downregulation is blocked by a rapamycin-insensitive p70S6K mutant and rescued by 4E-BP1 depletion. This represents a compensatory feedback where mTOR activity upregulates PHLPP to dampen Akt. Rapamycin treatment, mTOR siRNA knockdown, TSC2 siRNA, rapamycin-insensitive p70S6K mutant, 4E-BP1 siRNA, amino acid/glucose starvation The Journal of biological chemistry Medium 21177869
2020 FKBP51 canonical isoform mediates Akt ubiquitination at Lys63 via its TPR domain, an essential step for Akt activation. PHLPP silencing does not reduce Akt phosphorylation; instead PHLPP overexpression induces Akt phosphorylation by stabilizing the E3 ubiquitin ligase TRAF6 and supporting K63-ubiquitination of Akt. TPR domain mutant of FKBP51, ubiquitination assay (K63-specific), PHLPP silencing and overexpression, TRAF6 stability assay, FKBP51 interactome profiling from melanoma cells Cell death & disease Low 36781840

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth. Molecular cell 764 15808505
2007 Data growth and its impact on the SCOP database: new developments. Nucleic acids research 700 18000004
2004 SCOP database in 2004: refinements integrate structure and sequence family data. Nucleic acids research 671 14681400
2013 SCOPe: Structural Classification of Proteins--extended, integrating SCOP and ASTRAL data and classification of new structures. Nucleic acids research 527 24304899
2007 PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms. Molecular cell 493 17386267
2002 SCOP database in 2002: refinements accommodate structural genomics. Nucleic acids research 330 11752311
2020 The SCOP database in 2020: expanded classification of representative family and superfamily domains of known protein structures. Nucleic acids research 261 31724711
2015 Lysosomal mTORC2/PHLPP1/Akt Regulate Chaperone-Mediated Autophagy. Molecular cell 231 26118642
2007 The phosphatase PHLPP controls the cellular levels of protein kinase C. The Journal of biological chemistry 169 18162466
2019 LncRNA PCAT1 activates AKT and NF-κB signaling in castration-resistant prostate cancer by regulating the PHLPP/FKBP51/IKKα complex. Nucleic acids research 150 30773595
1999 SCOP: a Structural Classification of Proteins database. Nucleic acids research 148 9847194
2008 Loss of PHLPP expression in colon cancer: role in proliferation and tumorigenesis. Oncogene 138 19079341
2011 PTEN, NHERF1 and PHLPP form a tumor suppressor network that is disabled in glioblastoma. Oncogene 137 21804599
2014 Turning off AKT: PHLPP as a drug target. Annual review of pharmacology and toxicology 118 24392697
1999 A systematic comparison of protein structure classifications: SCOP, CATH and FSSP. Structure (London, England : 1993) 117 10508779
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
2014 Both decreased and increased SRPK1 levels promote cancer by interfering with PHLPP-mediated dephosphorylation of Akt. Molecular cell 112 24703948
2017 LncRNA MEG3 downregulation mediated by DNMT3b contributes to nickel malignant transformation of human bronchial epithelial cells via modulating PHLPP1 transcription and HIF-1α translation. Oncogene 105 28263966
2010 PHLPP-1 negatively regulates Akt activity and survival in the heart. Circulation research 105 20576936
2021 CircIL4R activates the PI3K/AKT signaling pathway via the miR-761/TRIM29/PHLPP1 axis and promotes proliferation and metastasis in colorectal cancer. Molecular cancer 100 34922544
2012 The deubiquitination enzyme USP46 functions as a tumor suppressor by controlling PHLPP-dependent attenuation of Akt signaling in colon cancer. Oncogene 99 22391563
2016 Xist reduction in breast cancer upregulates AKT phosphorylation via HDAC3-mediated repression of PHLPP1 expression. Oncotarget 96 27248326
2007 Proteolytic degradation of SCOP in the hippocampus contributes to activation of MAP kinase and memory. Cell 96 17382888
2011 miR-190-mediated downregulation of PHLPP contributes to arsenic-induced Akt activation and carcinogenesis. Toxicological sciences : an official journal of the Society of Toxicology 91 21750348
2012 Suppression of survival signalling pathways by the phosphatase PHLPP. The FEBS journal 89 22340730
2009 beta-TrCP-mediated ubiquitination and degradation of PHLPP1 are negatively regulated by Akt. Molecular and cellular biology 89 19797085
2011 The phosphatase PHLPP1 regulates Akt2, promotes pancreatic cancer cell death, and inhibits tumor formation. Gastroenterology 80 22044669
2020 The miR-92a-2-5p in exosomes from macrophages increases liver cancer cells invasion via altering the AR/PHLPP/p-AKT/β-catenin signaling. Cell death and differentiation 77 32587378
2011 PHLPP-mediated dephosphorylation of S6K1 inhibits protein translation and cell growth. Molecular and cellular biology 76 21986499
2014 PHLPP is a negative regulator of RAF1, which reduces colorectal cancer cell motility and prevents tumor progression in mice. Gastroenterology 75 24530606
2016 PHLPPing through history: a decade in the life of PHLPP phosphatases. Biochemical Society transactions 74 27913677
2013 Histone deacetylase 3 suppression increases PH domain and leucine-rich repeat phosphatase (Phlpp)1 expression in chondrocytes to suppress Akt signaling and matrix secretion. The Journal of biological chemistry 70 23408427
2010 Discovery of small molecule inhibitors of the PH domain leucine-rich repeat protein phosphatase (PHLPP) by chemical and virtual screening. Journal of medicinal chemistry 65 20836557
2014 MicroRNA-141 promotes the proliferation of non-small cell lung cancer cells by regulating expression of PHLPP1 and PHLPP2. FEBS letters 64 24945731
2011 Pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP): a new player in cell signaling. The Journal of biological chemistry 64 22144674
2015 MiR-199a-5p and miR-375 affect colon cancer cell sensitivity to cetuximab by targeting PHLPP1. Expert opinion on therapeutic targets 62 26107137
2013 WD repeat protein WDR48 in complex with deubiquitinase USP12 suppresses Akt-dependent cell survival signaling by stabilizing PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1). The Journal of biological chemistry 62 24145035
2011 Cutting edge: PHLPP regulates the development, function, and molecular signaling pathways of regulatory T cells. Journal of immunology (Baltimore, Md. : 1950) 62 21498666
2011 Scribble-mediated membrane targeting of PHLPP1 is required for its negative regulation of Akt. EMBO reports 61 21701506
2011 Increased levels of the Akt-specific phosphatase PH domain leucine-rich repeat protein phosphatase (PHLPP)-1 in obese participants are associated with insulin resistance. Diabetologia 60 21461637
2010 mTOR-dependent regulation of PHLPP expression controls the rapamycin sensitivity in cancer cells. The Journal of biological chemistry 60 21177869
2018 Activation of GSK3β/β-TrCP axis via PHLPP1 exacerbates Nrf2 degradation leading to impairment in cell survival pathway during diabetic nephropathy. Free radical biology & medicine 56 29655866
2020 Luteolin attenuates doxorubicin-induced cardiotoxicity by modulating the PHLPP1/AKT/Bcl-2 signalling pathway. PeerJ 52 32435528
2014 Physiological activation of Akt by PHLPP1 deletion protects against pathological hypertrophy. Cardiovascular research 52 25411382
2009 Systematic comparison of SCOP and CATH: a new gold standard for protein structure analysis. BMC structural biology 51 19374763
2013 Downregulation of PHLPP expression contributes to hypoxia-induced resistance to chemotherapy in colon cancer cells. Molecular and cellular biology 47 24061475
2015 Deletion of the PH-domain and Leucine-rich Repeat Protein Phosphatase 1 (Phlpp1) Increases Fibroblast Growth Factor (Fgf) 18 Expression and Promotes Chondrocyte Proliferation. The Journal of biological chemistry 45 25953896
2010 Protein phosphatase PHLPP1 controls the light-induced resetting of the circadian clock. Proceedings of the National Academy of Sciences of the United States of America 45 20080691
2019 Protein Kinase C Quality Control by Phosphatase PHLPP1 Unveils Loss-of-Function Mechanism in Cancer. Molecular cell 44 30904392
2013 NF-κB1 p50 promotes p53 protein translation through miR-190 downregulation of PHLPP1. Oncogene 44 23396362
2011 Mislocalization of the E3 ligase, β-transducin repeat-containing protein 1 (β-TrCP1), in glioblastoma uncouples negative feedback between the pleckstrin homology domain leucine-rich repeat protein phosphatase 1 (PHLPP1) and Akt. The Journal of biological chemistry 43 21454620
2015 Phlpp1 facilitates post-traumatic osteoarthritis and is induced by inflammation and promoter demethylation in human osteoarthritis. Osteoarthritis and cartilage 42 26746148
2012 PHLPP1 gene deletion protects the brain from ischemic injury. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 42 23072745
2019 Pink1 regulates FKBP5 interaction with AKT/PHLPP and protects neurons from neurotoxin stress induced by MPP. Journal of neurochemistry 40 30734931
2018 GYY4137 protects against myocardial ischemia/reperfusion injury via activation of the PHLPP-1/Akt/Nrf2 signaling pathway in diabetic mice. The Journal of surgical research 40 29605032
2013 Methanol extract from the stem of Cotinus coggygria Scop., and its major bioactive phytochemical constituent myricetin modulate pyrogallol-induced DNA damage and liver injury. Mutation research 39 23830930
2012 USP1 regulates AKT phosphorylation by modulating the stability of PHLPP1 in lung cancer cells. Journal of cancer research and clinical oncology 39 22426999
2015 Loss of PHLPP protects against colitis by inhibiting intestinal epithelial cell apoptosis. Biochimica et biophysica acta 38 26187040
2013 Vitamin E facilitates the inactivation of the kinase Akt by the phosphatase PHLPP1. Science signaling 37 23512990
2014 Crucial role of c-Jun phosphorylation at Ser63/73 mediated by PHLPP protein degradation in the cheliensisin a inhibition of cell transformation. Cancer prevention research (Philadelphia, Pa.) 35 25281487
2013 Oncogenic suppression of PHLPP1 in human melanoma. Oncogene 35 24121273
2020 Inhibition of PHLPP1 ameliorates cardiac dysfunction via activation of the PI3K/Akt/mTOR signalling pathway in diabetic cardiomyopathy. Journal of cellular and molecular medicine 32 32150791
2018 PHLPP1 mediates melanoma metastasis suppression through repressing AKT2 activation. Oncogene 32 29391600
2010 PHLPP1 splice variants differentially regulate AKT and PKCα signaling in hippocampal neurons: characterization of PHLPP proteins in the adult hippocampus. Journal of neurochemistry 30 20819118
2019 PHLPP1 counter-regulates STAT1-mediated inflammatory signaling. eLife 29 31408005
2017 PHLPP: a putative cellular target during insulin resistance and type 2 diabetes. The Journal of endocrinology 28 28428363
2016 Mutual inhibition of insulin signaling and PHLPP-1 determines cardioprotective efficiency of Akt in aged heart. Aging 28 27019292
2021 miR-190-5p Alleviates Myocardial Ischemia-Reperfusion Injury by Targeting PHLPP1. Disease markers 27 34868398
2018 ERK1/2 activated PHLPP1 induces skeletal muscle ER stress through the inhibition of a novel substrate AMPK. Biochimica et biophysica acta. Molecular basis of disease 27 29499326
2017 PHLPP regulates hexokinase 2-dependent glucose metabolism in colon cancer cells. Cell death discovery 27 28179998
2002 Automated assignment of SCOP and CATH protein structure classifications from FSSP scores. Proteins 27 11835515
2017 Phlpp inhibitors block pain and cartilage degradation associated with osteoarthritis. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 26 29068480
2019 Phlpp1 is associated with human intervertebral disc degeneration and its deficiency promotes healing after needle puncture injury in mice. Cell death & disease 25 31582730
2009 SCOP/PHLPP and its functional role in the brain. Molecular bioSystems 25 20024065
2017 SNORA74B gene silencing inhibits gallbladder cancer cells by inducing PHLPP and suppressing Akt/mTOR signaling. Oncotarget 24 28212545
2010 Reduced expression of the tumor suppressor PHLPP1 enhances the antiapoptotic B-cell receptor signal in chronic lymphocytic leukemia B-cells. Leukemia 24 20861921
2019 Deficiency in the phosphatase PHLPP1 suppresses osteoclast-mediated bone resorption and enhances bone formation in mice. The Journal of biological chemistry 22 31189651
2020 PHLPPing the Script: Emerging Roles of PHLPP Phosphatases in Cell Signaling. Annual review of pharmacology and toxicology 21 32997603
2019 CXCL13 is a differentiation- and hypoxia-induced adipocytokine that exacerbates the inflammatory phenotype of adipocytes through PHLPP1 induction. The Biochemical journal 21 31710352
2018 Clusterin enhances AKT2-mediated motility of normal and cancer prostate cells through a PTEN and PHLPP1 circuit. Journal of cellular physiology 21 30565691
2016 PHLPP negatively regulates cell motility through inhibition of Akt activity and integrin expression in pancreatic cancer cells. Oncotarget 21 26760962
2014 The N-terminal region of p27 inhibits HIF-1α protein translation in ribosomal protein S6-dependent manner by regulating PHLPP-Ras-ERK-p90RSK axis. Cell death & disease 21 25412313
2013 SGT1 regulates Akt signaling by promoting beta-TrCP-dependent PHLPP1 degradation in gastric cancer cells. Molecular biology reports 21 23440515
2021 Inhibition of PHLPP1/2 phosphatases rescues pancreatic β-cells in diabetes. Cell reports 20 34348155
2021 Downregulation of PHLPP induced by endoplasmic reticulum stress promotes eIF2α phosphorylation and chemoresistance in colon cancer. Cell death & disease 20 34663797
2020 Heat shock protein 47 promotes tumor survival and therapy resistance by modulating AKT signaling via PHLPP1 in colorectal cancer. Cancer biology & medicine 19 32587773
2020 P2 × 7 Receptor Inhibits Astroglial Autophagy via Regulating FAK- and PHLPP1/2-Mediated AKT-S473 Phosphorylation Following Kainic Acid-Induced Seizures. International journal of molecular sciences 19 32899862
2015 MiR-522 contributes to cell proliferation of human glioblastoma cells by suppressing PHLPP1 expression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 19 25776496
2010 Serine/threonine kinase akt activation regulates the activity of retinal serine/threonine phosphatases, PHLPP and PHLPPL. Journal of neurochemistry 18 20089132
2021 Reduced PHLPP Expression Leads to EGFR-TKI Resistance in Lung Cancer by Activating PI3K-AKT and MAPK-ERK Dual Signaling. Frontiers in oncology 17 34168988
2019 MIR-190B Alleviates Cell Autophagy and Burn-Induced Skeletal Muscle Wasting via Modulating PHLPP1/Akt/FoxO3A Signaling Pathway. Shock (Augusta, Ga.) 17 30407372
2016 Role of PHLPP1 in inflammation response: Its loss contributes to gliomas development and progression. International immunopharmacology 17 26971226
2014 A novel immunomodulatory function of PHLPP1: inhibition of iNOS via attenuation of STAT1 ser727 phosphorylation in mouse macrophages. Journal of leukocyte biology 17 24443556
2023 FKBP51 plays an essential role in Akt ubiquitination that requires Hsp90 and PHLPP. Cell death & disease 16 36781840
2022 PHLPP1 promotes neutral lipid accumulation through AMPK/ChREBP-dependent lipid uptake and fatty acid synthesis pathways. iScience 16 35141506
2019 Autophagy-mediated Mir6981 degradation exhibits CDKN1B promotion of PHLPP1 protein translation. Autophagy 16 30821592
2018 Silencing of PHLPP1 promotes neuronal apoptosis and inhibits functional recovery after spinal cord injury in mice. Life sciences 16 30114409
2016 Inhibitory Kinetics and Mechanism of Flavonoids Extracted from Cotinus coggygria Scop. Against Glioblastoma Cancer. Nutrition and cancer 16 27673410
2018 Acute Physiology and Neurologic Outcomes after Brain Injury in SCOP/PHLPP1 KO Mice. Scientific reports 15 29739983
2018 Tumor necrosis factor-alpha upregulated PHLPP1 through activating nuclear factor-kappa B during myocardial ischemia/reperfusion. Life sciences 15 29940243

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