Affinage

PTEN

Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN · UniProt P60484

Length
403 aa
Mass
47.2 kDa
Annotated
2026-06-10
100 papers in source corpus 23 papers cited in narrative 23 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

PTEN is a dual-specificity phosphatase that functions as a tumor suppressor primarily by antagonizing PI3K/Akt signaling (PMID:9861013, PMID:11395408). Its physiological substrate is the lipid second messenger PIP3, which it dephosphorylates at the D3 position to impair PDK1/Akt survival signaling; loss-of-function mutations elevate cellular PIP3 and constitutively activate Akt (PMID:11395408). Through this activity PTEN induces G1 cell cycle arrest, correlating with increased p27(KIP1) and decreased G1 CDK activity (PMID:9860981), and in PTEN-deficient cancers the residual pathway signaling becomes selectively dependent on the p110β (PIK3CB) PI3K isoform (PMID:18755892). Beyond its lipid phosphatase role, PTEN acts as a protein phosphatase on multiple substrates: it dephosphorylates FAK to inhibit cell spreading and migration (PMID:10547389), IRS1 to modulate insulin/IGF signaling (PMID:24814346), autophosphorylated PGK1 at Y324 to suppress glycolysis and tumor growth (PMID:31492635), Dishevelled to control cilia dynamics and WNT signaling (PMID:26399523), and γH2AX at DNA double-strand breaks to promote repair, where ATM-dependent phosphorylation and NSD2-mediated K349 methylation recognized by 53BP1 recruit PTEN to damage sites (PMID:31217297). Nuclear PTEN additionally supports genome stability at replication forks by stabilizing RPA1 and recruiting the deubiquitinase OTUB1 (PMID:26403191). PTEN activity and abundance are tightly regulated post-translationally—inhibited by PCAF-mediated acetylation of catalytic-cleft residues K125/K128 (PMID:16829519), inactivated by C-terminal tail phosphorylation that blocks membrane binding (PMID:31636093) and by ROS-driven Cys71–Cys124 disulfide oxidation (protected by peroxiredoxin) (PMID:33669370), stabilized by USP13-mediated deubiquitylation (PMID:24270891), and destabilized in the nucleus by FBXO22-mediated ubiquitylation (PMID:32249768), with nuclear import controlled by monoubiquitylation (PMID:18216329). A homeostatic mTOR/4E-BP1 translational feedback loop further tunes PTEN expression to limit pathway duration (PMID:33606974).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    Establishing that PTEN negatively regulates the PI3K/Akt axis defined its core signaling function and placed it upstream of Akt.

    Evidence Dominant-negative catalytically inactive mutant with Akt and 4E-BP1 phosphorylation readouts in cells

    PMID:9860981 PMID:9861013

    Open questions at the time
    • Did not identify the direct molecular substrate
    • Mechanism of growth suppression linked correlatively to p27(KIP1)
  2. 2001 High

    Identifying PIP3 as the physiological substrate revealed the biochemical basis of PTEN tumor suppression, showing it dephosphorylates the D3 position to antagonize PDK1/Akt.

    Evidence In vitro biochemical phosphatase and substrate-specificity assays; PIP3 measurement in mutant cells

    PMID:11395408

    Open questions at the time
    • Did not address PTEN protein-substrate (non-lipid) activities
    • Membrane-recruitment dynamics not resolved here
  3. 1999 Medium

    Demonstrating direct dephosphorylation of FAK extended PTEN function to a protein phosphatase controlling adhesion and migration.

    Evidence Protein phosphatase assay on FAK plus migration/invasion assays with PTEN expression

    PMID:10547389

    Open questions at the time
    • Consolidated review evidence rather than single definitive study
    • Cellular context dependence of FAK targeting unresolved
  4. 2000 Medium

    Showing that C-terminal PDZ-binding interactions are phosphorylation-regulated revealed how PTEN scaffolding and partner choice are dynamically controlled.

    Evidence Yeast two-hybrid, peptide pulldown, and binding assays with hDLG/hMAST205 PDZ domains

    PMID:10646847

    Open questions at the time
    • Identity of the ~90/120 kDa phospho-promoted partners not established
    • Functional consequence of PDZ binding not defined
  5. 2001 Medium

    Defining mutual PTEN–androgen receptor repression connected PTEN signaling to hormone-driven prostate cancer proliferation.

    Evidence PTEN re-expression, PI3K inhibition, AR reporter and apoptosis assays in prostate cells

    PMID:11278645

    Open questions at the time
    • AKT-independent protective arm mechanistically undefined
    • Single cell-type context
  6. 2006 High

    PCAF-mediated acetylation of catalytic-cleft lysines established a growth-factor-responsive switch that inhibits PTEN lipid phosphatase activity.

    Evidence Co-IP, PCAF knockdown, K125R/K128R mutagenesis, phosphatase and cell cycle assays

    PMID:16829519

    Open questions at the time
    • Deacetylase reversing the mark not identified here
    • In vivo relevance not tested
  7. 2008 Medium

    Multiple regulatory mechanisms were resolved—isoform-selective PI3K dependency, redox inactivation, C-terminal tail autoinhibition, and monoubiquitylation-driven nuclear import—mapping how PTEN function is spatially and biochemically controlled.

    Evidence Isoform shRNA with xenografts; oxidation/Prx assays; structural/mutagenesis review; ubiquitination and fractionation assays

    PMID:18216329 PMID:18755892 PMID:31636093 PMID:33669370

    Open questions at the time
    • Some mechanisms derived from consolidated review evidence
    • Coordination between tail phosphorylation, oxidation, and localization not integrated
  8. 2008 Medium

    Discovery of the Akt-EGR1-ARF-PTEN feedback loop showed how PTEN transcription is induced downstream of its own pathway.

    Evidence Kinase and sumoylation assays, ARF-knockout mice, EGR1 phospho-site mutagenesis

    PMID:19057511

    Open questions at the time
    • Quantitative contribution to PTEN homeostasis unclear
    • Tissue specificity of the loop not defined
  9. 2009 Medium

    Identifying a >600-kDa PTEN-associated complex containing p85 and p110β revealed direct physical engagement with the PI3K machinery.

    Evidence Reciprocal Co-IP and sucrose-gradient fractionation; trastuzumab-modulated association in ERBB2 cells

    PMID:19635806

    Open questions at the time
    • Structural architecture of the complex unknown
    • Functional consequence of p85 binding for phosphatase activity unresolved
  10. 2013 High

    USP13 was identified as a deubiquitylase that directly stabilizes PTEN, defining a stability control node whose loss drives AKT-dependent tumor growth.

    Evidence DUB screen, Co-IP, in vitro deubiquitylation, knockdown/overexpression, tumor growth assays

    PMID:24270891

    Open questions at the time
    • Opposing E3 ligase context not fully mapped here
    • Compartment specificity of USP13 action unexplored
  11. 2014 Medium

    PTEN was established as the direct IRS1 phosphatase and as an ER/MAM-localized regulator of IP3R-dependent Ca2+ release, broadening its protein-substrate repertoire and apoptotic control.

    Evidence Biochemical dephosphorylation and reconstitution with NEDD4/PTEN genetics; fractionation and IP3R Co-IP with Ca2+/apoptosis assays

    PMID:24814346 PMID:25312582

    Open questions at the time
    • MAM findings partly from consolidated review evidence
    • Structural basis of IP3R interaction unknown
  12. 2015 Medium

    Identification of DVL and RPA1 engagement linked PTEN protein-phosphatase and scaffolding activity to ciliogenesis/WNT signaling and to replication-fork protection.

    Evidence Loss-of-function phosphorylation assays on DVL; Co-IP, iPOND, STORM, and OTUB1-mediated RPA1 deubiquitination assays

    PMID:26399523 PMID:26403191

    Open questions at the time
    • Direct vs indirect DVL dephosphorylation not fully resolved
    • How PTEN recruits OTUB1 mechanistically undefined
  13. 2019 High

    Defining PTEN dephosphorylation of PGK1 Y324 and recruitment to DSBs via NSD2/53BP1 established its roles in suppressing glycolysis and promoting DNA repair through protein-phosphatase activity.

    Evidence Co-IP, in vitro dephosphorylation, PGK1 Y324F knockin mice, tumor specimens; methylation, γH2AX dephosphorylation assays and xenografts

    PMID:31217297 PMID:31492635

    Open questions at the time
    • Interplay between metabolic and DNA-repair functions not integrated
    • Relative contributions of lipid vs protein phosphatase activity in tumors unresolved
  14. 2020 High

    Compartment-specific nuclear degradation by FBXO22 and the PTEN-FOXO1-BACH1/MAFF proteasome-repression axis revealed how nuclear PTEN levels and a targetable proteasome dependency are controlled.

    Evidence Ubiquitination assays with K221R mutagenesis and fractionation; ChIP, reporter, PDX and autochthonous mouse models

    PMID:32249768 PMID:32967970

    Open questions at the time
    • Signals triggering nuclear FBXO22 activity unknown
    • Generality of proteasome dependency across PTEN-null cancers untested
  15. 2021 High

    Demonstrating mTOR/4E-BP1-dependent translational upregulation of PTEN defined a homeostatic feedback loop limiting PI3K pathway duration.

    Evidence 4E-BP1 deletion, mTOR/PI3K inhibition, polysome profiling, signaling readouts

    PMID:33606974

    Open questions at the time
    • Quantitative dynamics of the feedback loop in vivo unclear
    • Tissue-specific dependence not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PTEN's many regulatory layers and substrate choices are integrated into a single coordinated tumor-suppressive program across compartments remains unresolved.
  • No unified model coordinating acetylation, oxidation, tail phosphorylation, and localization
  • Relative in vivo importance of lipid vs protein phosphatase substrates undefined
  • Mechanisms directing PTEN to specific compartmental substrates unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016787 hydrolase activity 4 GO:0008289 lipid binding 2
Localization
GO:0005634 nucleus 4 GO:0005783 endoplasmic reticulum 1 GO:0005829 cytosol 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-73894 DNA Repair 2 R-HSA-1430728 Metabolism 1 R-HSA-1640170 Cell Cycle 1 R-HSA-5357801 Programmed Cell Death 1
Partners
FBXO22ITPR1MDC1PCAFPIK3CBPIK3R1RPA1USP13
Complex memberships
PTEN-associated complex (PAC; with p85/p110β)

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 PTEN/MMAC1 acts as a negative regulator of the PI3K/Akt pathway: it impairs activation of endogenous Akt, inhibits phosphorylation of 4E-BP1, and a catalytically inactive dominant-negative PTEN mutant enhances 4E-BP1 phosphorylation, placing PTEN upstream of Akt in the PI3K pathway. Biochemical assays in cells; catalytically inactive dominant-negative mutant; Akt activity measurement; 4E-BP1 phosphorylation assay Proceedings of the National Academy of Sciences of the United States of America High 9861013
1998 PTEN/MMAC1 expression induces G1 cell cycle arrest in human glioblastoma cells, correlating with increased p27(KIP1) and decreased G1 cyclin-dependent kinase activities; this effect is mimicked by the PI3K inhibitor LY294002 and is accompanied by inhibition of Akt, placing PTEN upstream of PI3K/Akt→p27(KIP1) in G1 control. PTEN re-expression in U87MG cells; cell cycle analysis; Western blotting for p27(KIP1), CDK activity assays; PI3K inhibitor LY294002 comparison Proceedings of the National Academy of Sciences of the United States of America High 9860981
2001 PTEN's physiological substrate is phosphatidylinositol 3,4,5-trisphosphate (PIP3); PTEN specifically dephosphorylates the D3 position of PIP3, thereby negatively regulating PDK1/Akt survival signaling. Mutations impairing PTEN function markedly increase cellular PIP3 levels and constitutively activate Akt. Biochemical phosphatase assays; substrate specificity experiments; lipid phosphatase activity measurement Annual review of biochemistry High 11395408
2006 PCAF histone acetyltransferase physically interacts with PTEN and acetylates lysine residues K125 and K128 within PTEN's catalytic cleft in a growth-factor-dependent manner. Acetylation of PTEN inhibits its lipid phosphatase activity toward PIP3, reducing its ability to block PI3K signaling and G1 arrest. Acetylation-resistant K125R/K128R PTEN mutants retain phosphatase activity in the presence of enforced PCAF. Co-immunoprecipitation; shRNA knockdown of PCAF; site-directed mutagenesis (K125R, K128R); phosphatase activity assays; cell cycle analysis The Journal of biological chemistry High 16829519
2000 PTEN PDZ-binding domain (C-terminal) interacts with PDZ domains of hDLG and hMAST205; threonine phosphorylation of this domain inhibits binding to hDLG and hMAST205 PDZ domains but promotes binding to other proteins (~90 and ~120 kDa) from cell lysate, demonstrating phosphorylation-dependent modulation of PTEN protein-protein interactions. Yeast two-hybrid; microtiter plate binding assays; synthetic peptide co-precipitation from A431 cell lysate; anti-hDLG Western blot Cancer research Medium 10646847
2008 In PTEN-deficient cancers, growth and PI3K pathway signaling depend on PIK3CB (p110β) rather than PIK3CA (p110α); shRNA-mediated depletion of PIK3CB (but not PIK3CA) inhibits downstream PI3K signaling and cell growth in PTEN-null cancer cells, both in vitro and in vivo, and this function requires p110β lipid kinase activity. Lentiviral inducible shRNA knockdown of PI3K isoforms; PI3K signaling readouts (pAKT); cell growth assays; in vivo xenograft models Proceedings of the National Academy of Sciences of the United States of America High 18755892
2009 PTEN physically associates with the regulatory subunit p85 of PI3K; this association involves the unphosphorylated form of PTEN residing in a >600-kDa PTEN-associated complex (PAC) that also includes the p110β isoform of PI3K. The PTEN-p85 association is enhanced by trastuzumab and linked to decreased AKT phosphorylation in ERBB2-amplified breast cancer cells. Co-immunoprecipitation with newly generated antibodies; sucrose gradient fractionation to identify PAC; Western blotting for pAKT Molecular and cellular biology Medium 19635806
2013 USP13 is a deubiquitylase that directly binds PTEN, removes its polyubiquitin chains, and stabilizes PTEN protein. Loss of USP13 in breast cancer cells promotes AKT phosphorylation, cell proliferation, and tumor growth through PTEN downregulation; this effect is PTEN-dependent. DUB screen (30 enzymes); co-immunoprecipitation; in vitro deubiquitylation assay; USP13 knockdown/overexpression; AKT phosphorylation; tumor growth assays Nature cell biology High 24270891
2014 PTEN functions as a protein tyrosine phosphatase that selectively dephosphorylates IRS1 (insulin receptor substrate-1). Loss of NEDD4 (a PTEN ubiquitin ligase that promotes PTEN degradation) causes defective IGF signaling including IRS1 and AKT phosphorylation, which is rescued by PTEN ablation. Direct biochemical and cellular reconstitution confirmed PTEN as the IRS1 phosphatase. Direct biochemical dephosphorylation assay; cellular reconstitution; NEDD4 and PTEN knockouts/knockdowns; IRS1 phosphorylation Western blot Nature structural & molecular biology High 24814346
2019 PTEN protein phosphatase activity directly dephosphorylates autophosphorylated PGK1 at Y324, thereby inhibiting PGK1 kinase activity, glycolysis, and ATP production. PTEN physically interacts with PGK1. Knockin expression of PGK1 Y324F (phospho-resistant) inhibits brain tumor formation, and PGK1 Y324 phosphorylation inversely correlates with PTEN expression in glioblastoma specimens. Co-immunoprecipitation; in vitro dephosphorylation assay; PGK1 Y324F knockin mouse model; glycolysis/ATP assays; human tumor specimen analysis Molecular cell High 31492635
2019 DNA double-strand breaks (DSBs) promote ATM-dependent phosphorylation of PTEN at T/S398, which enhances PTEN interaction with MDC1. DSBs also induce NSD2-mediated dimethylation of PTEN at K349; this methylation mark is recognized by the tudor domain of 53BP1 to recruit PTEN to DNA-damage sites, where PTEN's protein phosphatase activity governs efficient DSB repair partly through dephosphorylation of γH2AX. Co-immunoprecipitation; phosphoproteomics; site-directed mutagenesis of K349; in vitro methylation assay; γH2AX dephosphorylation assay; in vivo xenograft models Cancer discovery High 31217297
2015 PTEN controls the phosphorylation state of Dishevelled (DVL) and thereby regulates multicilia formation and cilia disassembly. PTEN is required for convergent extension movements. DVL is identified as a protein substrate of PTEN, coupling PTEN to regulation of cilia dynamics and WNT signaling. Loss-of-function studies (PTEN knockout/knockdown); phosphorylation assays on DVL; cilia formation and disassembly assays; convergent extension assays Nature communications Medium 26399523
2015 PTEN is physically associated with RPA1 (replication protein A 1) via the RPA1 C-terminal domain; PTEN localizes at replication forks (confirmed by iPOND) and promotes RPA1 accumulation there. PTEN recruits the deubiquitinase OTUB1 to mediate RPA1 deubiquitination. Loss of PTEN leads to replication fork collapse and chromosomal instability under replication stress. Co-immunoprecipitation; STORM super-resolution microscopy; iPOND (isolation of proteins on nascent DNA); RPA1 deubiquitination assay; chromosomal instability assays in PTEN-KO cells Cell research High 26403191
2008 PTEN enters the nucleus by monoubiquitylation-dependent import (as well as by simple diffusion and active shuttling). Nuclear PTEN plays roles in chromosome stability and DNA repair distinct from cytoplasmic PTEN's role as a PI3K/AKT pathway negative regulator. Cytoplasmic localization signal-dependent export also regulates PTEN compartmentalization. Ubiquitination assays; nuclear/cytoplasmic fractionation; chromosomal stability assays; genetic studies (referenced primary papers: Wang et al. 2007, Trotman et al. 2007, Shen et al. 2007) Journal of cell science Medium 18216329
2020 FBXO22 ubiquitylates nuclear PTEN specifically at lysine 221, leading to its proteasomal degradation. FBXO22 acts on nuclear but not cytoplasmic PTEN, identifying a compartment-specific E3 ubiquitin ligase for PTEN. Co-immunoprecipitation; ubiquitination assays; site-directed mutagenesis (K221R); nuclear/cytoplasmic fractionation; FBXO22 knockdown/overexpression in colorectal cancer cells Nature communications High 32249768
2008 PTEN active-site cysteine is oxidized by reactive oxygen species forming an intramolecular disulfide bond between Cys124 and Cys71, which inactivates PTEN. Peroxiredoxin I (Prx I) protects PTEN from oxidation under moderate oxidative stress through direct interaction, preserving PTEN tumor-suppressive function. Prx II deficiency increases PTEN oxidation and insulin sensitivity. PTEN oxidation assays; Prx knockout/knockdown cell systems; direct binding assays; insulin signaling readouts Antioxidants (Basel, Switzerland) Medium 33669370
2021 PI3K/mTOR-dependent signaling controls PTEN protein expression through mTOR/4E-BP1-mediated translational regulation. Deletion of 4E-BP1 abolishes translational upregulation of PTEN by PI3K, establishing a homeostatic feedback loop: PI3K activation increases PTEN translation to limit pathway duration. 4E-BP1 deletion; mTOR inhibitor treatment; polysome profiling/translational assays; PI3K inhibitor treatment; signaling readouts (pAKT, pS6K) Molecular cell High 33606974
2008 PTEN activity is regulated by C-terminal tail (CTT) phosphorylation at serine/threonine residues: phosphorylation of the unstructured CTT promotes interaction with the phosphatase-C2 superdomain and inactivates PTEN by preventing membrane association. Unphosphorylated PTEN is the active, membrane-associated form. Structural analysis; phosphorylation site mutagenesis; membrane-binding and activity assays (referenced in review of structural mechanisms) Cold Spring Harbor perspectives in medicine Medium 31636093
2001 PTEN and androgen receptor (AR) mutually repress each other in prostate cancer cells: PTEN (and PI3K inhibition) represses AR transcriptional activity and androgen-induced proliferation likely via AKT downregulation, while androgens protect from PTEN-induced apoptosis in an AR-dependent but AKT-independent manner. PTEN re-expression; PI3K inhibitor; reporter assays for AR transcriptional activity; PSA production assay; apoptosis assays The Journal of biological chemistry Medium 11278645
2008 PTEN promotes EGR1 sumoylation via the Akt-EGR1-ARF-PTEN axis: Akt phosphorylates EGR1 at S350 and T309, promoting EGR1 interaction with ARF and sumoylation by the ARF/Ubc9/SUMO system. EGR1 sumoylation is required for PTEN transcriptional induction. ARF-deficient mice show reduced EGR1 sumoylation and reduced PTEN levels, establishing a feedback loop. Kinase assay; sumoylation assay; co-immunoprecipitation; ARF knockout mice; site-directed mutagenesis of EGR1 phosphorylation sites The EMBO journal Medium 19057511
2020 PTEN promotes nuclear translocation of FOXO1 in cholangiocarcinoma cells. Nuclear FOXO1 increases expression of BACH1 and MAFF, which directly repress transcription of proteasome subunit genes. Loss of PTEN thus upregulates proteasome expression and activity, creating a dependency on proteasome function in PTEN-deficient cancers. PTEN knockdown/overexpression; nuclear fractionation; ChIP; reporter assays for proteasome gene promoters; PDX models; autochthonous mouse models Science translational medicine High 32967970
1999 PTEN directly dephosphorylates tyrosine-phosphorylated focal adhesion kinase (FAK), thereby inhibiting integrin-triggered signaling, focal adhesion formation, cell spreading, and cell migration. Protein phosphatase assay on FAK substrate; cell migration/invasion assays with PTEN expression Journal of the National Cancer Institute Medium 10547389
2014 PTEN localizes to the endoplasmic reticulum (ER) and mitochondria-associated membranes (MAMs), where it interacts with inositol 1,4,5-trisphosphate receptors (IP3Rs) and regulates Ca2+ release from the ER, thereby controlling sensitivity to apoptosis via its protein phosphatase activity. Subcellular fractionation; co-immunoprecipitation with IP3R; Ca2+ release measurements; apoptosis assays Methods (San Diego, Calif.) Medium 25312582

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems. Proceedings of the National Academy of Sciences of the United States of America 805 9990064
2003 PTEN: one gene, many syndromes. Human mutation 598 12938083
1998 The PTEN/MMAC1 tumor suppressor phosphatase functions as a negative regulator of the phosphoinositide 3-kinase/Akt pathway. Proceedings of the National Academy of Sciences of the United States of America 570 9861013
1998 Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer through loss of expression. Proceedings of the National Academy of Sciences of the United States of America 544 9560261
2014 PTEN. Annual review of biochemistry 484 24905788
2008 PTEN-deficient cancers depend on PIK3CB. Proceedings of the National Academy of Sciences of the United States of America 472 18755892
2009 PI3K/PTEN signaling in angiogenesis and tumorigenesis. Advances in cancer research 463 19595306
1997 MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines. Cancer research 431 9393738
1998 PTEN/MMAC1/TEP1 suppresses the tumorigenicity and induces G1 cell cycle arrest in human glioblastoma cells. Proceedings of the National Academy of Sciences of the United States of America 425 9860981
1999 Mutational spectra of PTEN/MMAC1 gene: a tumor suppressor with lipid phosphatase activity. Journal of the National Cancer Institute 415 10564676
1997 Disruption of the MMAC1/PTEN gene by deletion or mutation is a frequent event in malignant melanoma. Cancer research 414 9288767
1997 Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease. Human molecular genetics 397 9259288
2001 PTEN and myotubularin: novel phosphoinositide phosphatases. Annual review of biochemistry 390 11395408
2015 PTEN: Multiple Functions in Human Malignant Tumors. Frontiers in oncology 365 25763354
2002 Protean PTEN: form and function. American journal of human genetics 349 11875759
2003 PTEN signaling pathways in melanoma. Oncogene 344 12789288
2007 PTEN, more than the AKT pathway. Carcinogenesis 338 17341655
2008 PTEN: a new guardian of the genome. Oncogene 298 18794879
2003 PTEN: from pathology to biology. Trends in cell biology 285 12946627
2007 PI3K/PTEN signaling in tumorigenesis and angiogenesis. Biochimica et biophysica acta 280 17964232
2000 Mutations of the human PTEN gene. Human mutation 266 10923032
2014 PTEN function: the long and the short of it. Trends in biochemical sciences 249 24656806
2008 The nuclear affairs of PTEN. Journal of cell science 243 18216329
1997 Mutation analysis of the putative tumor suppressor gene PTEN/MMAC1 in primary breast carcinomas. Cancer research 238 9288766
2019 The PTEN⁻PI3K Axis in Cancer. Biomolecules 237 30999672
2010 PTEN/mTOR and axon regeneration. Experimental neurology 236 20079353
2000 PTEN, a unique tumor suppressor gene. Endocrine-related cancer 231 10903528
2019 The Clinical Spectrum of PTEN Mutations. Annual review of medicine 206 31433956
2010 PI(3)king apart PTEN's role in cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 205 20622047
2008 PTEN signaling in brain: neuropathology and tumorigenesis. Oncogene 191 18794877
2008 Understanding PTEN regulation: PIP2, polarity and protein stability. Oncogene 190 18794881
2006 PCAF modulates PTEN activity. The Journal of biological chemistry 190 16829519
1998 Identification of PTEN/MMAC1 alterations in uncultured melanomas and melanoma cell lines. Oncogene 189 9692547
2000 Relative reciprocity of NRAS and PTEN/MMAC1 alterations in cutaneous melanoma cell lines. Cancer research 184 10766161
2013 Deubiquitylation and stabilization of PTEN by USP13. Nature cell biology 181 24270891
2008 PTEN hamartoma tumor syndromes. European journal of human genetics : EJHG 180 18781191
2019 PTEN Suppresses Glycolysis by Dephosphorylating and Inhibiting Autophosphorylated PGK1. Molecular cell 178 31492635
1998 Mutation analysis of the PTEN/MMAC1 gene in lung cancer. Oncogene 171 9794233
1997 PTEN/MMAC1 mutations and EGFR amplification in glioblastomas. Cancer research 171 9393744
2006 Regulation of the PTEN phosphatase. Gene 162 16675164
1999 PTEN gene and integrin signaling in cancer. Journal of the National Cancer Institute 158 10547389
1998 Point mutation and homozygous deletion of PTEN/MMAC1 in primary bladder cancers. Oncogene 153 9671402
2002 Pten signaling in gliomas. Neuro-oncology 147 12084351
1998 PTEN/MMAC1 mutations identified in small cell, but not in non-small cell lung cancers. Oncogene 146 9696041
2012 PTEN signaling in autism spectrum disorders. Current opinion in neurobiology 145 22664040
1998 PTEN gene alterations in lymphoid neoplasms. Blood 145 9787181
2000 Threonine phosphorylation of the MMAC1/PTEN PDZ binding domain both inhibits and stimulates PDZ binding. Cancer research 141 10646847
1998 Inactivation of the PTEN/MMAC1/TEP1 gene in human lung cancers. Genes, chromosomes & cancer 136 9598803
2007 PTEN enters the nuclear age. Cell 134 17218252
2018 Gene-specific criteria for PTEN variant curation: Recommendations from the ClinGen PTEN Expert Panel. Human mutation 130 30311380
2012 PTEN in DNA damage repair. Cancer letters 127 22266095
2015 Focus on PTEN Regulation. Frontiers in oncology 122 26284192
1999 PTEN/MMAC1/TEP1 in signal transduction and tumorigenesis. European journal of biochemistry 118 10469123
2011 Genetic alterations of PTEN in human melanoma. Cellular and molecular life sciences : CMLS 117 22076652
2008 PTEN regulation by Akt-EGR1-ARF-PTEN axis. The EMBO journal 116 19057511
2021 Regulation of PTEN translation by PI3K signaling maintains pathway homeostasis. Molecular cell 111 33606974
2014 The PTEN/NRF2 axis promotes human carcinogenesis. Antioxidants & redox signaling 109 24892215
2013 When overgrowth bumps into cancer: the PTEN-opathies. American journal of medical genetics. Part C, Seminars in medical genetics 105 23613428
2003 PTEN methylation and expression in glioblastomas. Acta neuropathologica 105 12904991
1999 PTEN/MMAC1 mutations in hepatocellular carcinomas. Oncogene 105 10340391
2014 PTEN is a protein tyrosine phosphatase for IRS1. Nature structural & molecular biology 102 24814346
2015 PTEN ceRNA networks in human cancer. Methods (San Diego, Calif.) 101 25644446
2019 PTEN in Autism and Neurodevelopmental Disorders. Cold Spring Harbor perspectives in medicine 95 31427284
2013 Genomic Rearrangements of PTEN in Prostate Cancer. Frontiers in oncology 92 24062990
2003 Physiological functions of Pten in mouse tissues. Cell structure and function 92 12655146
2008 Post-translational regulation of PTEN. Oncogene 87 18794880
2000 MMAC1/PTEN inhibits cell growth and induces chemosensitivity to doxorubicin in human bladder cancer cells. Oncogene 86 11103942
2001 Antagonism between PTEN/MMAC1/TEP-1 and androgen receptor in growth and apoptosis of prostatic cancer cells. The Journal of biological chemistry 83 11278645
2020 Regulatory role of microRNAs on PTEN signaling. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 82 33166764
2017 Cell Cycle Control by PTEN. Journal of molecular biology 80 28602818
2015 PTEN regulates RPA1 and protects DNA replication forks. Cell research 80 26403191
2009 p85 Associates with unphosphorylated PTEN and the PTEN-associated complex. Molecular and cellular biology 80 19635806
2020 FBXO22 degrades nuclear PTEN to promote tumorigenesis. Nature communications 79 32249768
2017 PTEN proteoforms in biology and disease. Cellular and molecular life sciences : CMLS 78 28289760
2008 Portrait of PTEN: messages from mutant mice. Cancer science 76 18201277
2017 PTEN, Insulin Resistance and Cancer. Current pharmaceutical design 73 28677502
2019 PTEN Methylation by NSD2 Controls Cellular Sensitivity to DNA Damage. Cancer discovery 72 31217297
2006 Tumours and tremors: how PTEN regulation underlies both. British journal of cancer 69 16495927
2001 PTEN/MMAC1/TEP1 mutations in human primary renal-cell carcinomas and renal carcinoma cell lines. International journal of cancer 69 11146448
2018 Regulation of PTEN expression by noncoding RNAs. Journal of experimental & clinical cancer research : CR 67 30217221
2010 PTEN in liver diseases and cancer. World journal of gastroenterology 65 20872961
2008 Regulation of T-cell responses by PTEN. Immunological reviews 65 18759931
2020 Structural Mechanisms of PTEN Regulation. Cold Spring Harbor perspectives in medicine 64 31636093
2020 The Role of PTEN in Neurodevelopment. Molecular neuropsychiatry 61 32399470
2018 Regulation and modulation of PTEN activity. Molecular biology reports 61 30145641
2001 PTEN/MMAC1 in malignant melanoma and its importance for tumor progression. Cancer genetics and cytogenetics 60 11297763
2000 Mutation analysis of PTEN/MMAC1 in acute myeloid leukemia. American journal of hematology 60 10706759
2020 The PTEN Conundrum: How to Target PTEN-Deficient Prostate Cancer. Cells 59 33105713
2014 Study of PTEN subcellular localization. Methods (San Diego, Calif.) 59 25312582
2014 Posttranslational regulation of phosphatase and tensin homolog (PTEN) and its functional impact on cancer behaviors. Drug design, development and therapy 58 25336918
2013 PTEN modulators: a patent review. Expert opinion on therapeutic patents 58 23379765
2007 PTEN: its deregulation and tumorigenesis. Biological & pharmaceutical bulletin 58 17827710
1998 Alterations of PTEN/MMAC1, a candidate tumor suppressor gene, and its homologue, PTH2, in small cell lung cancer cell lines. Oncogene 57 9467947
2019 PTEN and Gynecological Cancers. Cancers 54 31569439
2015 PTEN regulates cilia through Dishevelled. Nature communications 54 26399523
2021 Redox Regulation of PTEN by Peroxiredoxins. Antioxidants (Basel, Switzerland) 50 33669370
2020 PTEN in Hereditary and Sporadic Cancer. Cold Spring Harbor perspectives in medicine 49 31570378
2020 PTEN status determines chemosensitivity to proteasome inhibition in cholangiocarcinoma. Science translational medicine 47 32967970
1998 Mutational analysis of the PTEN/MMAC1 gene in non-Hodgkin's lymphoma. Leukemia 47 9697884
2008 PTEN mutation: many birds with one stone in tumorigenesis. Anticancer research 45 19189642

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