CoChat
Sign Up
Cited by 309PI3K/AKT/mTOR signaling in cancerProtein Tyrosine PhosphatasesProtein Kinase Regulation and GTPase Signaling

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

PTEN function: the long and the short of it

Open access
Hopkins, Benjamin D., Hodakoski, Cindy, Barrows, Douglas, Mense, Sarah M., Parsons, Ramon E.·2014·Trends in Biochemical Sciences
DOI 10.1016/j.tibs.2014.02.006PMC PMC4043120
Open this paper in CoChat — free account

Abstract

Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a phosphatase that is frequently altered in cancer. PTEN has phosphatase-dependent and -independent roles, and genetic alterations in PTEN lead to deregulation of protein synthesis, the cell cycle, migration, growth, DNA repair, and survival signaling. PTEN localization, stability, conformation, and phosphatase activity are controlled by an array of protein-protein interactions and post-translational modifications. Thus, PTEN-interacting and -modifying proteins have profound effects on the tumor suppressive functions of PTEN. Moreover, recent studies identified mechanisms by which PTEN can exit cells, via either exosomal export or secretion, and act on neighboring cells. This review focuses on modes of PTEN protein regulation and ways in which perturbations in this regulation may lead to disease.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.tibs.2014.02.006

Cites

0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Show all 6 references

Research works printed but not linked: 81

  1. Li, 1997, PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer, Science, 275, 1943, 10.1126/science.275.5308.1943 · DOI · Paper page
  2. Steck, 1997, Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23. 3 that is mutated in multiple advanced cancers, Nat. Genet., 15, 356, 10.1038/ng0497-356 · DOI
  3. Gao, 2013, Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal, Sci. Signal., 6, pl1, 10.1126/scisignal.2004088 · DOI · Paper page
  4. Li, 1997, TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta, Cancer Res., 57, 2124
  5. Myers, 1998, The lipid phosphatase activity of PTEN is critical for its tumor supressor function, Proc. Natl. Acad. Sci. U.S.A., 95, 13513, 10.1073/pnas.95.23.13513 · DOI
  6. Maehama, 1998, The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate, J. Biol. Chem., 273, 13375, 10.1074/jbc.273.22.13375 · DOI · Paper page
  7. Stambolic, 1998, Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN, Cell, 95, 29, 10.1016/S0092-8674(00)81780-8 · DOI · Paper page
  8. Leslie, 2007, PtdIns(3,4,5)P3-dependent and -independent roles for PTEN in the control of cell migration, Curr. Biol., 17, 115, 10.1016/j.cub.2006.12.026 · DOI
  9. Raftopoulou, 2004, Regulation of cell migration by the C2 domain of the tumor suppressor PTEN, Science, 303, 1179, 10.1126/science.1092089 · DOI
  10. Dey, 2008, The protein phosphatase activity of PTEN regulates SRC family kinases and controls glioma migration, Cancer Res., 68, 1862, 10.1158/0008-5472.CAN-07-1182 · DOI
  11. Tamura, 1998, Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN, Science, 280, 1614, 10.1126/science.280.5369.1614 · DOI · Paper page
  12. Cully, 2006, Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis, Nat. Rev. Cancer, 6, 184, 10.1038/nrc1819 · DOI
  13. Mayo, 2002, The PTEN, Mdm2, p53 tumor suppressor-oncoprotein network, Trends Biochem. Sci., 27, 462, 10.1016/S0968-0004(02)02166-7 · DOI
  14. Alimonti, 2010, Subtle variations in Pten dose determine cancer susceptibility, Nat. Genet., 42, 454, 10.1038/ng.556 · DOI
  15. Shen-Li, 2010, Reduction of Pten dose leads to neoplastic development in multiple organs of Pten (shRNA) mice, Cancer Biol. Ther., 10, 1194, 10.4161/cbt.10.11.13814 · DOI
  16. Liaw, 1997, Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome, Nat. Genet., 16, 64, 10.1038/ng0597-64 · DOI
  17. Arch, 1997, Deletion of PTEN in a patient with Bannayan–Riley–Ruvalcaba syndrome suggests allelism with Cowden disease, Am. J. Med. Genet., 71, 489, 10.1002/(SICI)1096-8628(19970905)71:4<489::AID-AJMG24>3.0.CO;2-B · DOI
  18. Zhou, 2001, Association of germline mutation in the PTEN tumour suppressor gene and Proteus and Proteus-like syndromes, Lancet, 358, 210, 10.1016/S0140-6736(01)05412-5 · DOI
  19. Marsh, 1998, Allelic imbalance, including deletion of PTEN/MMACI, at the Cowden disease locus on 10q22-23, in hamartomas from patients with Cowden syndrome and germline PTEN mutation, Genes Chromosomes Cancer, 21, 61, 10.1002/(SICI)1098-2264(199801)21:1<61::AID-GCC8>3.0.CO;2-6 · DOI
  20. Zhou, 2003, Germline inactivation of PTEN and dysregulation of the phosphoinositol-3-kinase/Akt pathway cause human Lhermitte–Duclos disease in adults, Am. J. Hum. Genet., 73, 1191, 10.1086/379382 · DOI
  21. Butler, 2005, Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations, J. Med. Genet., 42, 318, 10.1136/jmg.2004.024646 · DOI · Paper page
  22. Hollander, 2011, PTEN loss in the continuum of common cancers, rare syndromes and mouse models, Nat. Rev. Cancer, 11, 289, 10.1038/nrc3037 · DOI
  23. Trimboli, 2009, Pten in stromal fibroblasts suppresses mammary epithelial tumours, Nature, 461, 1084, 10.1038/nature08486 · DOI
  24. Lee, 1999, Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association, Cell, 99, 323, 10.1016/S0092-8674(00)81663-3 · DOI
  25. Walker, 2004, The tumour-suppressor function of PTEN requires an N-terminal lipid-binding motif, Biochem. J., 379, 301, 10.1042/bj20031839 · DOI
  26. Campbell, 2003, Allosteric activation of PTEN phosphatase by phosphatidylinositol 4,5-bisphosphate, J. Biol. Chem., 278, 33617, 10.1074/jbc.C300296200 · DOI
  27. Vazquez, 2000, Phosphorylation of the PTEN tail regulates protein stability and function, Mol. Cell. Biol., 20, 5010, 10.1128/MCB.20.14.5010-5018.2000 · DOI
  28. Lee, 2002, Reversible inactivation of the tumor suppressor PTEN by H2O2, J. Biol. Chem., 277, 20336, 10.1074/jbc.M111899200 · DOI
  29. Silva, 2008, PTEN posttranslational inactivation and hyperactivation of the PI3K/Akt pathway sustain primary T cell leukemia viability, J. Clin. Invest., 118, 3762, 10.1172/JCI34616 · DOI
  30. Okumura, 2006, PCAF modulates PTEN activity, J. Biol. Chem., 281, 26562, 10.1074/jbc.M605391200 · DOI
  31. Ikenoue, 2008, PTEN acetylation modulates its interaction with PDZ domain, Cancer Res., 68, 6908, 10.1158/0008-5472.CAN-08-1107 · DOI
  32. Wang, 2007, NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN, Cell, 128, 129, 10.1016/j.cell.2006.11.039 · DOI
  33. Fouladkou, 2008, The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization, Proc. Natl. Acad. Sci. U.S.A., 105, 8585, 10.1073/pnas.0803233105 · DOI
  34. Drinjakovic, 2010, E3 ligase Nedd4 promotes axon branching by downregulating PTEN, Neuron, 65, 341, 10.1016/j.neuron.2010.01.017 · DOI
  35. Van Themsche, 2009, X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization, J. Biol. Chem., 284, 20462, 10.1074/jbc.C109.009522 · DOI
  36. Maddika, 2011, WWP2 is an E3 ubiquitin ligase for PTEN, Nat. Cell Biol., 13, 728, 10.1038/ncb2240 · DOI
  37. Lee, 2013, RFP-mediated ubiquitination of PTEN modulates its effect on AKT activation, Cell Res., 23, 552, 10.1038/cr.2013.27 · DOI
  38. Maccario, 2010, Ubiquitination of PTEN (phosphatase and tensin homolog) inhibits phosphatase activity and is enhanced by membrane targeting and hyperosmotic stress, J. Biol. Chem., 285, 12620, 10.1074/jbc.M109.072280 · DOI
  39. Huang, 2012, SUMO1 modification of PTEN regulates tumorigenesis by controlling its association with the plasma membrane, Nat. Commun., 3, 911, 10.1038/ncomms1919 · DOI
  40. Bassi, 2013, Nuclear PTEN controls DNA repair and sensitivity to genotoxic stress, Science, 341, 395, 10.1126/science.1236188 · DOI · Paper page
  41. Miller, 2002, Direct identification of PTEN phosphorylation sites, FEBS Lett., 528, 145, 10.1016/S0014-5793(02)03274-X · DOI
  42. Torres, 2001, The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at its C terminus. Implications for PTEN stability to proteasome-mediated degradation, J. Biol. Chem., 276, 993, 10.1074/jbc.M009134200 · DOI
  43. Al-Khouri, 2005, Cooperative phosphorylation of the tumor suppressor phosphatase and tensin homologue (PTEN) by casein kinases and glycogen synthase kinase 3beta, J. Biol. Chem., 280, 35195, 10.1074/jbc.M503045200 · DOI
  44. Koul, 2002, Motif analysis of the tumor suppressor gene MMAC/PTEN identifies tyrosines critical for tumor suppression and lipid phosphatase activity, Oncogene, 21, 2357, 10.1038/sj.onc.1205296 · DOI
  45. Lu, 2003, Src family protein-tyrosine kinases alter the function of PTEN to regulate phosphatidylinositol 3-kinase/AKT cascades, J. Biol. Chem., 278, 40057, 10.1074/jbc.M303621200 · DOI
  46. Li, 2005, Regulation of PTEN by Rho small GTPases, Nat. Cell Biol., 7, 399, 10.1038/ncb1236 · DOI
  47. Yim, 2009, Rak functions as a tumor suppressor by regulating PTEN protein stability and function, Cancer Cell, 15, 304, 10.1016/j.ccr.2009.02.012 · DOI
  48. Maccario, 2007, PTEN is destabilized by phosphorylation on Thr366, Biochem. J., 405, 439, 10.1042/BJ20061837 · DOI
  49. Odriozola, 2007, Regulation of PTEN activity by its carboxyl-terminal autoinhibitory domain, J. Biol. Chem., 282, 23306, 10.1074/jbc.M611240200 · DOI
  50. Tibarewal, 2012, PTEN protein phosphatase activity correlates with control of gene expression and invasion, a tumor-suppressing phenotype, but not with AKT activity, Sci. Signal., 5, ra18, 10.1126/scisignal.2002138 · DOI
  51. Zhang, 2012, Functional analysis of the protein phosphatase activity of PTEN, Biochem. J., 444, 457, 10.1042/BJ20120098 · DOI
  52. Rahdar, 2009, A phosphorylation-dependent intramolecular interaction regulates the membrane association and activity of the tumor suppressor PTEN, Proc. Natl. Acad. Sci. U.S.A., 106, 480, 10.1073/pnas.0811212106 · DOI
  53. Tolkacheva, 2001, Regulation of PTEN binding to MAGI-2 by two putative phosphorylation sites at threonine 382 and 383, Cancer Res., 61, 4985
  54. Vazquez, 2001, Phosphorylation of the PTEN tail acts as an inhibitory switch by preventing its recruitment into a protein complex, J. Biol. Chem., 276, 48627, 10.1074/jbc.C100556200 · DOI
  55. Okumura, 2005, Cellular transformation by the MSP58 oncogene is inhibited by its physical interaction with the PTEN tumor suppressor, Proc. Natl. Acad. Sci. U.S.A., 102, 2703, 10.1073/pnas.0409370102 · DOI
  56. Torres, 2003, Phosphorylation-regulated cleavage of the tumor suppressor PTEN by caspase-3: implications for the control of protein stability and PTEN–protein interactions, J. Biol. Chem., 278, 30652, 10.1074/jbc.M212610200 · DOI
  57. Ning, 2006, A novel leptin signalling pathway via PTEN inhibition in hypothalamic cell lines and pancreatic beta-cells, EMBO J., 25, 2377, 10.1038/sj.emboj.7601118 · DOI
  58. Moult, 2010, Leptin regulates AMPA receptor trafficking via PTEN inhibition, J. Neurosci., 30, 4088, 10.1523/JNEUROSCI.3614-09.2010 · DOI
  59. Patsoukis, 2013, PD-1 increases PTEN phosphatase activity while decreasing PTEN protein stability by inhibiting casein kinase 2, Mol. Cell. Biol., 33, 3091, 10.1128/MCB.00319-13 · DOI
  60. Yang, 2013, Reduced expression of PTEN and increased PTEN phosphorylation at residue Ser380 in gastric cancer tissues: a novel mechanism of PTEN inactivation, Clin. Res. Hepatol. Gastroenterol., 37, 72, 10.1016/j.clinre.2012.03.002 · DOI
  61. Vo, 2011, Targeting notch pathway enhances rapamycin antitumor activity in pancreas cancers through PTEN phosphorylation, Mol. Cancer, 10, 138, 10.1186/1476-4598-10-138 · DOI
  62. Lima-Fernandes, 2011, Distinct functional outputs of PTEN signalling are controlled by dynamic association with beta-arrestins, EMBO J., 30, 2557, 10.1038/emboj.2011.178 · DOI
  63. Wu, 2000, Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2, Proc. Natl. Acad. Sci. U.S.A., 97, 4233, 10.1073/pnas.97.8.4233 · DOI
  64. Wu, 2000, Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of MAGI3, a novel membrane-associated guanylate kinase, J. Biol. Chem., 275, 21477, 10.1074/jbc.M909741199 · DOI
  65. Kotelevets, 2005, Implication of the MAGI-1b/PTEN signalosome in stabilization of adherens junctions and suppression of invasiveness, FASEB J., 19, 115, 10.1096/fj.04-1942fje · DOI
  66. Takahashi, 2006, PTEN tumor suppressor associates with NHERF proteins to attenuate PDGF receptor signaling, EMBO J., 25, 910, 10.1038/sj.emboj.7600979 · DOI
  67. Chagpar, 2010, Direct positive regulation of PTEN by the p85 subunit of phosphatidylinositol 3-kinase, Proc. Natl. Acad. Sci. U.S.A., 107, 5471, 10.1073/pnas.0908899107 · DOI
  68. Cheung, 2011, High frequency of PIK3R1 and PIK3R2 mutations in endometrial cancer elucidates a novel mechanism for regulation of PTEN protein stability, Cancer Discov., 1, 170, 10.1158/2159-8290.CD-11-0039 · DOI
  69. Sumitomo, 2004, Synergy in tumor suppression by direct interaction of neutral endopeptidase with PTEN, Cancer Cell, 5, 67, 10.1016/S1535-6108(03)00331-3 · DOI
  70. Fine, 2009, Activation of the PI3K pathway in cancer through inhibition of PTEN by exchange factor P-REX2a, Science, 325, 1261, 10.1126/science.1173569 · DOI
  71. Hodakoski, 2014, Regulation of PTEN inhibition by the pleckstrin homology domain of P-REX2 during insulin signaling and glucose homeostasis, Proc. Natl. Acad. Sci. U.S.A., 111, 155, 10.1073/pnas.1213773111 · DOI
  72. He, 2010, Shank-interacting protein-like 1 promotes tumorigenesis via PTEN inhibition in human tumor cells, J. Clin. Invest., 120, 2094, 10.1172/JCI40778 · DOI
  73. Wang, 2013, Dual functions for cytosolic alpha-mannosidase (Man2C1): its down-regulation causes mitochondria-dependent apoptosis independently of its alpha-mannosidase activity, J. Biol. Chem., 288, 11887, 10.1074/jbc.M112.425702 · DOI
  74. Yue, 2004, Suppression of 6A8 alpha-mannosidase gene expression reduced the potentiality of growth and metastasis of human nasopharyngeal carcinoma, Int. J. Cancer, 108, 189, 10.1002/ijc.11536 · DOI
  75. Tian, 2008, Inhibition of alpha-mannosidase Man2c1 gene expression suppresses growth of esophageal carcinoma cells through mitotic arrest and apoptosis, Cancer Sci., 99, 2428, 10.1111/j.1349-7006.2008.01019.x · DOI
  76. Xiang, 2010, hMan2c1 transgene promotes tumor progress in mice, Transgenic Res., 19, 67, 10.1007/s11248-009-9299-3 · DOI
  77. He, 2011, α-Mannosidase 2C1 attenuates PTEN function in prostate cancer cells, Nat. Commun., 2, 307, 10.1038/ncomms1309 · DOI
  78. Song, 2011, Nuclear PTEN regulates the APC–CDH1 tumor-suppressive complex in a phosphatase-independent manner, Cell, 144, 187, 10.1016/j.cell.2010.12.020 · DOI
  79. Putz, 2012, The tumor suppressor PTEN is exported in exosomes and has phosphatase activity in recipient cells, Sci. Signal., 5, ra70, 10.1126/scisignal.2003084 · DOI
  80. Hopkins, 2013, A secreted PTEN phosphatase that enters cells to alter signaling and survival, Science, 341, 399, 10.1126/science.1234907 · DOI
  81. Malaney, 2013, The PTEN Long N-tail is intrinsically disordered: increased viability for PTEN therapy, Mol. Biosyst., 9, 2877, 10.1039/c3mb70267g · DOI

Cited by

Sorted by citations

Items 201–281 of 281

Metadata

Authors
Hopkins, B. D., Hodakoski, C., Barrows, D., Mense, S. M., & Parsons, R. E.
Affiliations
Icahn School of Medicine at Mount Sinai (US)
Corresponding author
Parsons, Ramon E.
ORCID
Venue
Trends in Biochemical Sciences
Publisher
Elsevier BV
Published
2014-04
Volume
39
Issue
4
Pages
183-190
ISSN
0968-0004 (ISSN-L)
DOI
10.1016/j.tibs.2014.02.006
PMC
PMC4043120
OpenAlex
W2109559424
Cited by
309
References
125
Citations by year
2026: 13 · 2025: 26 · 2024: 29 · 2023: 21 · 2022: 24 · 2021: 35 · 2020: 36 · 2019: 32 · 2018: 22 · 2017: 22 · 2016: 13 · 2015: 25 · 2014: 11
FWCI
2.23
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Trends in Biochemical Sciences (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (P01CA097403, R01CA082783, R01CA155117, R01CA184016)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
PTEN, phosphatase and tensin homolog, tumor suppressor, phosphatase activity, protein-protein interaction, post-translational modification, protein stability, cancer, cell cycle regulation, DNA repair, cell migration
MeSH terms
Animals, Cell Cycle, Gene Expression Regulation, Humans, Protein Processing, Post-Translational, Genomic Instability, PTEN Phosphohydrolase

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review