PTEN (gene)

Last updated
PTEN
Pten.jpg
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases PTEN , 10q23del, BZS, CWS1, DEC, GLM2, MHAM, MMAC1, PTEN1, TEP1, phosphatase and tensin homolog, Phosphatase and tensin homolog, PTENbeta
External IDs OMIM: 601728 MGI: 109583 HomoloGene: 265 GeneCards: PTEN
Orthologs
SpeciesHumanMouse
Entrez

5728

19211

Ensembl

ENSG00000171862
ENSG00000284792

ENSMUSG00000013663

UniProt

P60484

O08586

RefSeq (mRNA)

NM_000314
NM_001304717
NM_001304718

NM_008960
NM_177096

RefSeq (protein)

NP_000305
NP_001291646
NP_001291647
NP_000305.3

NP_032986

Location (UCSC) Chr 10: 87.86 – 87.97 Mb Chr 19: 32.73 – 32.8 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse
Space-filling model of the PTEN protein (blue) complexed with tartaric acid (brown). PTEN protein (space-filling model).png
Space-filling model of the PTEN protein (blue) complexed with tartaric acid (brown).

Phosphatase and tensin homolog (PTEN) is a phosphatase in humans and is encoded by the PTEN gene. [6] Mutations of this gene are a step in the development of many cancers, specifically glioblastoma, lung cancer, breast cancer, and prostate cancer. Genes corresponding to PTEN (orthologs) [7] have been identified in most mammals for which complete genome data are available.

Contents

PTEN acts as a tumor suppressor gene through the action of its phosphatase protein product. This phosphatase is involved in the regulation of the cell cycle, preventing cells from growing and dividing too rapidly. [8] It is a target of many anticancer drugs.

The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin-like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating the Akt/PKB signaling pathway. [9]

Function

PTEN protein acts as a phosphatase to dephosphorylate phosphatidylinositol (3,4,5)-trisphosphate (PtdIns (3,4,5)P3 or PIP3). PTEN specifically catalyses the dephosphorylation of the 3` phosphate of the inositol ring in PIP3, resulting in the biphosphate product PIP2 (PtdIns(4,5)P2). This dephosphorylation is important because it results in inhibition of the Akt signaling pathway, which plays an important role in regulating cellular behaviors such as cell growth, survival, and migration.

PTEN also has weak protein phosphatase activity, but this activity is also crucial for its role as a tumor suppressor. PTEN's protein phosphatase activity may be involved in the regulation of the cell cycle, preventing cells from growing and dividing too rapidly. [8] There have been numerous reported protein substrates for PTEN, including IRS1 [10] and Dishevelled. [11]

PTEN is one of the targets for drug candidates such as the oncomiR, MIRN21.

Structure

The structure of the core of PTEN (solved by X-ray crystallography, see figure to the upper right [5] ) reveals that it consists primarily of a phosphatase domain, and a C2 domain: the phosphatase domain contains the active site, which carries out the enzymatic function of the protein, while the C2 domain binds the phospholipid membrane. Thus PTEN binds the membrane through both its phosphatase and C2 domains, bringing the active site to the membrane-bound PIP3 to dephosphorylate it.

The two domains of PTEN, a protein tyrosine phosphatase domain and a C2 domain, are inherited together as a single unit and thus constitute a superdomain, not only in PTEN but also in various other proteins in fungi, plants and animals, for example, tensin proteins and auxilin. [12]

The active site of PTEN consists of three loops, the TI Loop, the P Loop, and the WPD Loop, all named following the PTPB1 nomenclature. [5] Together they form an unusually deep and wide pocket which allows PTEN to accommodate the bulky phosphatidylinositol 3,4,5-trisphosphate substrate. The dephosphorylation reaction mechanism of PTEN is thought to proceed through a phosphoenzyme intermediate, with the formation of a phosphodiester bond on the active site cysteine, C124.

Not present in the crystal structure of PTEN is a short 10-amino-acid unstructured region N-terminal of the phosphatase domain (from residues 6 to 15), known variously as the PIP2 Binding Domain (PBD) or PIP2 Binding Motif (PBM) [13] [14] [15] This region increases PTEN's affinity for the plasma membrane by binding to Phosphatidylinositol 4,5-bisphosphate, or possibly any anionic lipid.

Also not present in the crystal structure is the intrinsically disordered C-terminal region (CTR) (spanning residues 353–403). The CTR is constitutively phosphorylated at various positions that effect various aspects of PTEN, including its ability to bind to lipid membranes, and also act as either a protein or lipid phosphatase. [16] [17]

Additionally, PTEN can also be expressed as PTEN-L [18] (known as PTEN-Long, or PTEN-α [19] ), a leucine initiator alternative start site variant, which adds an additional 173 amino acids to the N-terminus of PTEN. The exact role of this 173-amino acid extension is not yet known, either causing PTEN to be secreted from the cell, or to interact with the mitochondria. The N-terminal extension has been predicted to be largely disordered, [20] although there is evidence that there is some structure in the last twenty amino acids of the extension (most proximal to the start methionine of PTEN). [17]

Clinical significance

Cancer

PTEN is one of the most commonly lost tumor suppressors in human cancer; in fact, up to 70% of men with prostate cancer are estimated to have lost a copy of the PTEN gene at the time of diagnosis. [21] A number of studies have found increased frequency of PTEN loss in tumours which are more highly visible on diagnostic scans such as mpMRI, potentially reflecting increased proliferation and cell density in these tumours. [22]

During tumor development, mutations and deletions of PTEN occur that inactivate its enzymatic activity leading to increased cell proliferation and reduced cell death. Frequent genetic inactivation of PTEN occurs in glioblastoma, endometrial cancer, and prostate cancer; and reduced expression is found in many other tumor types such as lung and breast cancer. Furthermore, PTEN mutation also causes a variety of inherited predispositions to cancer.

Non-cancerous neoplasia

Researchers have identified more than 70 mutations in the PTEN gene in people with Cowden syndrome.[ citation needed ] These mutations can be changes in a small number of base pairs or, in some cases, deletions of a large number of base pairs.[ citation needed ] Most of these mutations cause the PTEN gene to make a protein that does not function properly or does not work at all. The defective protein is unable to stop cell division or signal abnormal cells to die, which can lead to tumor growth, particularly in the breast, thyroid, or uterus. [23]

Mutations in the PTEN gene cause several other disorders that, like Cowden syndrome, are characterized by the development of non-cancerous tumors called hamartomas. These disorders include Bannayan–Riley–Ruvalcaba syndrome and Proteus-like syndrome. Together, the disorders caused by PTEN mutations are called PTEN hamartoma tumor syndromes, or PHTS. Mutations responsible for these syndromes cause the resulting protein to be non-functional or absent. The defective protein allows the cell to divide in an uncontrolled way and prevents damaged cells from dying, which can lead to the growth of tumors. [23]

Brain function and autism

Defects of the PTEN gene have been cited to be a potential cause of autism spectrum disorders. [24]

When defective, PTEN protein interacts with the protein of a second gene known as Tp53 to dampen energy production in neurons. This severe stress leads to a spike in harmful mitochondrial DNA changes and abnormal levels of energy production in the cerebellum and hippocampus, brain regions critical for social behavior and cognition. When PTEN protein is insufficient, its interaction with p53 triggers deficiencies and defects in other proteins that also have been found in patients with learning disabilities including autism. [24] People with autism and PTEN mutations may have macrocephaly (unusually large heads). [25]

Patients with defective PTEN can develop cerebellar mass lesions called dysplastic gangliocytomas or Lhermitte–Duclos disease. [23]

Cell regeneration

PTEN's strong link to cell growth inhibition is being studied as a possible therapeutic target in tissues that do not traditionally regenerate in mature animals, such as central neurons. PTEN deletion mutants have recently [26] been shown to allow nerve regeneration in mice. [27] [28]

As a drug target

PTEN inhibitors

Bisperoxovanadium compounds may have a neuroprotective effect after CNS injury. [29] PTEN is inhibited by sarcopoterium. [30]

Cell lines

Cell lines with known PTEN mutations include:

Interactions

PTEN (gene) has been shown to interact with:

See also

Related Research Articles

<span class="mw-page-title-main">Benign tumor</span> Mass of cells which cannot spread throughout the body

A benign tumor is a mass of cells (tumor) that does not invade neighboring tissue or metastasize. Compared to malignant (cancerous) tumors, benign tumors generally have a slower growth rate. Benign tumors have relatively well differentiated cells. They are often surrounded by an outer surface or stay contained within the epithelium. Common examples of benign tumors include moles and uterine fibroids.

<span class="mw-page-title-main">Protein kinase B</span> Set of three serine/threonine-specific protein kinases

Protein kinase B (PKB), also known as Akt, is the collective name of a set of three serine/threonine-specific protein kinases that play key roles in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration.

<span class="mw-page-title-main">Cowden syndrome</span> Medical condition

Cowden syndrome is an autosomal dominant inherited condition characterized by benign overgrowths called hamartomas as well as an increased lifetime risk of breast, thyroid, uterine, and other cancers. It is often underdiagnosed due to variability in disease presentation, but 99% of patients report mucocutaneous symptoms by age 20–29. Despite some considering it a primarily dermatologic condition, Cowden's syndrome is a multi-system disorder that also includes neurodevelopmental disorders such as macrocephaly.

<span class="mw-page-title-main">Phosphatidylinositol (3,4,5)-trisphosphate</span> Chemical compound

Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases' (PI 3-kinases) phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PIP2). It is a phospholipid that resides on the plasma membrane.

<span class="mw-page-title-main">Phosphoinositide 3-kinase</span> Class of enzymes

Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer.

<span class="mw-page-title-main">Phosphatidylinositol 3,4-bisphosphate</span>

Phosphatidylinositol (3,4)-bisphosphate is a minor phospholipid component of cell membranes, yet an important second messenger. The generation of PtdIns(3,4)P2 at the plasma membrane activates a number of important cell signaling pathways.

<span class="mw-page-title-main">Bannayan–Riley–Ruvalcaba syndrome</span> Medical condition

Bannayan–Riley–Ruvalcaba syndrome (BRRS) is a rare overgrowth syndrome and hamartomatous disorder with occurrence of multiple subcutaneous lipomas, macrocephaly and hemangiomas. The disease is inherited in an autosomal dominant manner. The disease belongs to a family of hamartomatous polyposis syndromes, which also includes Peutz–Jeghers syndrome, juvenile polyposis and Cowden syndrome. Mutation of the PTEN gene underlies this syndrome, as well as Cowden syndrome, Proteus syndrome, and Proteus-like syndrome, these four syndromes are referred to as PTEN Hamartoma-Tumor Syndromes.

<span class="mw-page-title-main">CHEK2</span> Protein-coding gene in humans

CHEK2 is a tumor suppressor gene that encodes the protein CHK2, a serine-threonine kinase. CHK2 is involved in DNA repair, cell cycle arrest or apoptosis in response to DNA damage. Mutations to the CHEK2 gene have been linked to a wide range of cancers.

The enzyme phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase (EC 3.1.3.67) catalyzes the chemical reaction

<span class="mw-page-title-main">PTPRK</span> Protein-coding gene in the species Homo sapiens

Receptor-type tyrosine-protein phosphatase kappa is an enzyme that in humans is encoded by the PTPRK gene. PTPRK is also known as PTPkappa and PTPκ.

<span class="mw-page-title-main">PTENP1</span>

Phosphatase and tensin homolog, pseudogene 1, also known as PTENP1, is a human pseudogene. which has a partial reactivated function as a competing endogenous RNA regulating the tumor suppressor gene PTEN.

<span class="mw-page-title-main">TPTE</span> Protein-coding gene in the species Homo sapiens

Putative tyrosine-protein phosphatase TPTE is an enzyme that in humans is encoded by the TPTE gene.

The Akt signaling pathway or PI3K-Akt signaling pathway is a signal transduction pathway that promotes survival and growth in response to extracellular signals. Key proteins involved are PI3K and Akt.

<span class="mw-page-title-main">Phosphoinositide-dependent kinase-1</span> Protein-coding gene in the species Homo sapiens

In the field of biochemistry, PDPK1 refers to the protein 3-phosphoinositide-dependent protein kinase-1, an enzyme which is encoded by the PDPK1 gene in humans. It is implicated in the development and progression of melanomas.

<span class="mw-page-title-main">PI3K/AKT/mTOR pathway</span> Cell cycle regulation pathway

The PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in regulating the cell cycle. Therefore, it is directly related to cellular quiescence, proliferation, cancer, and longevity. PI3K activation phosphorylates and activates AKT, localizing it in the plasma membrane. AKT can have a number of downstream effects such as activating CREB, inhibiting p27, localizing FOXO in the cytoplasm, activating PtdIns-3ps, and activating mTOR which can affect transcription of p70 or 4EBP1. There are many known factors that enhance the PI3K/AKT pathway including EGF, shh, IGF-1, insulin, and CaM. Both leptin and insulin recruit PI3K signalling for metabolic regulation. The pathway is antagonized by various factors including PTEN, GSK3B, and HB9.

<span class="mw-page-title-main">Rho-associated protein kinase</span>

Rho-associated protein kinase (ROCK) is a kinase belonging to the AGC family of serine-threonine specific protein kinases. It is involved mainly in regulating the shape and movement of cells by acting on the cytoskeleton.

Tensin was first identified as a 220 kDa multi-domain protein localized to the specialized regions of plasma membrane called integrin-mediated focal adhesions. Genome sequencing and comparison have revealed the existence of four tensin genes in humans. These genes appear to be related by ancient instances of gene duplication.

72 kDa inositol polyphosphate 5-phosphatase, also known as phosphatidylinositol-4,5-bisphosphate 5-phosphatase or Pharbin, is an enzyme that in humans is encoded by the INPP5E gene.

<span class="mw-page-title-main">Voltage sensitive phosphatase</span> Class of enzymes

Voltage sensitive phosphatases or voltage sensor-containing phosphatases, commonly abbreviated VSPs, are a protein family found in many species, including humans, mice, zebrafish, frogs, and sea squirt.

<span class="mw-page-title-main">GSDMD</span> Protein found in humans

Gasdermin D (GSDMD) is a protein that in humans is encoded by the GSDMD gene on chromosome 8. It belongs to the gasdermin family which is conserved among vertebrates and comprises six members in humans, GSDMA, GSDMB, GSDMC, GSDMD, GSDME (DFNA5) and DFNB59 (Pejvakin). Members of the gasdermin family are expressed in a variety of cell types including epithelial cells and immune cells. GSDMA, GSDMB, GSDMC, GSDMD and GSDME have been suggested to act as tumour suppressors.

References

  1. 1 2 3 ENSG00000284792 GRCh38: Ensembl release 89: ENSG00000171862, ENSG00000284792 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000013663 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 Lee JO, Yang H, Georgescu MM, Di Cristofano A, Maehama T, Shi Y, et al. (October 1999). "Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association". Cell. 99 (3): 323–334. doi: 10.1016/S0092-8674(00)81663-3 . PMID   10555148. S2CID   5624414.
  6. ↑ Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, et al. (April 1997). "Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers". Nature Genetics. 15 (4): 356–362. doi:10.1038/ng0497-356. PMID   9090379. S2CID   41286105.
  7. ↑ "OrthoMaM phylogenetic marker: PTEN coding sequence". Archived from the original on 2016-12-27. Retrieved 2009-12-02.
  8. 1 2 Chu EC, Tarnawski AS (October 2004). "PTEN regulatory functions in tumor suppression and cell biology". Medical Science Monitor. 10 (10): RA235–RA241. PMID   15448614.
  9. ↑ "Entrez Gene: PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1)".
  10. ↑ Shi Y, Wang J, Chandarlapaty S, Cross J, Thompson C, Rosen N, Jiang X (June 2014). "PTEN is a protein tyrosine phosphatase for IRS1". Nature Structural & Molecular Biology. 21 (6): 522–527. doi:10.1038/nsmb.2828. PMC   4167033 . PMID   24814346.
  11. ↑ Shnitsar I, Bashkurov M, Masson GR, Ogunjimi AA, Mosessian S, Cabeza EA, et al. (September 2015). "PTEN regulates cilia through Dishevelled". Nature Communications. 6: 8388. Bibcode:2015NatCo...6.8388S. doi:10.1038/ncomms9388. PMC   4598566 . PMID   26399523.
  12. ↑ Haynie DT, Xue B (May 2015). "Superdomains in the protein structure hierarchy: The case of PTP-C2". Protein Science. 24 (5): 874–882. doi:10.1002/pro.2664. PMC   4420535 . PMID   25694109.
  13. ↑ Campbell RB, Liu F, Ross AH (September 2003). "Allosteric activation of PTEN phosphatase by phosphatidylinositol 4,5-bisphosphate". The Journal of Biological Chemistry. 278 (36): 33617–33620. doi: 10.1074/jbc.C300296200 . PMID   12857747.
  14. ↑ Iijima M, Huang YE, Luo HR, Vazquez F, Devreotes PN (April 2004). "Novel mechanism of PTEN regulation by its phosphatidylinositol 4,5-bisphosphate binding motif is critical for chemotaxis". The Journal of Biological Chemistry. 279 (16): 16606–16613. doi: 10.1074/jbc.M312098200 . PMID   14764604.
  15. ↑ McConnachie G, Pass I, Walker SM, Downes CP (May 2003). "Interfacial kinetic analysis of the tumour suppressor phosphatase, PTEN: evidence for activation by anionic phospholipids". The Biochemical Journal. 371 (Pt 3): 947–955. doi:10.1042/BJ20021848. PMC   1223325 . PMID   12534371.
  16. ↑ Rahdar M, Inoue T, Meyer T, Zhang J, Vazquez F, Devreotes PN (January 2009). "A phosphorylation-dependent intramolecular interaction regulates the membrane association and activity of the tumor suppressor PTEN". Proceedings of the National Academy of Sciences of the United States of America. 106 (2): 480–485. Bibcode:2009PNAS..106..480R. doi: 10.1073/pnas.0811212106 . PMC   2626728 . PMID   19114656.
  17. 1 2 Masson GR, Perisic O, Burke JE, Williams RL (January 2016). "The intrinsically disordered tails of PTEN and PTEN-L have distinct roles in regulating substrate specificity and membrane activity". The Biochemical Journal. 473 (2): 135–144. doi:10.1042/BJ20150931. PMC   4700475 . PMID   26527737.
  18. ↑ Hopkins BD, Fine B, Steinbach N, Dendy M, Rapp Z, Shaw J, et al. (July 2013). "A secreted PTEN phosphatase that enters cells to alter signaling and survival". Science. 341 (6144): 399–402. Bibcode:2013Sci...341..399H. doi:10.1126/science.1234907. PMC   3935617 . PMID   23744781.
  19. ↑ Liang H, He S, Yang J, Jia X, Wang P, Chen X, et al. (May 2014). "PTENα, a PTEN isoform translated through alternative initiation, regulates mitochondrial function and energy metabolism". Cell Metabolism. 19 (5): 836–848. doi:10.1016/j.cmet.2014.03.023. PMC   4097321 . PMID   24768297.
  20. ↑ Malaney P, Uversky VN, Davé V (November 2013). "The PTEN Long N-tail is intrinsically disordered: increased viability for PTEN therapy". Molecular BioSystems. 9 (11): 2877–2888. doi:10.1039/c3mb70267g. PMID   24056727.
  21. ↑ Chen Z, Trotman LC, Shaffer D, Lin HK, Dotan ZA, Niki M, et al. (August 2005). "Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis". Nature. 436 (7051): 725–730. Bibcode:2005Natur.436..725C. doi:10.1038/nature03918. PMC   1939938 . PMID   16079851.
  22. ↑ Norris JM, Simpson BS, Parry MA, Allen C, Ball R, Freeman A, et al. (July 2020). "Genetic Landscape of Prostate Cancer Conspicuity on Multiparametric Magnetic Resonance Imaging: A Systematic Review and Bioinformatic Analysis". European Urology Open Science. 20: 37–47. doi: 10.1016/j.euros.2020.06.006 . PMC   7497895 . PMID   33000006.
  23. 1 2 3 Pilarski R, Eng C (May 2004). "Will the real Cowden syndrome please stand up (again)? Expanding mutational and clinical spectra of the PTEN hamartoma tumour syndrome". Journal of Medical Genetics. 41 (5): 323–326. doi:10.1136/jmg.2004.018036. PMC   1735782 . PMID   15121767.
  24. 1 2 Napoli E, Ross-Inta C, Wong S, Hung C, Fujisawa Y, Sakaguchi D, et al. (2012). "Mitochondrial dysfunction in Pten haplo-insufficient mice with social deficits and repetitive behavior: interplay between Pten and p53". PLOS ONE. 7 (8): e42504. Bibcode:2012PLoSO...742504N. doi: 10.1371/journal.pone.0042504 . PMC   3416855 . PMID   22900024.
  25. ↑ Charney, Dennis S.; Sklar, Pamela B.; Nestler, Eric J.; Buxbaum, Joseph D. (2018). Charney & Nestler's Neurobiology of Mental Illness. Oxford University Press. p. 846. ISBN   9780190681425.
  26. ↑ "Rodent of the Week: Nerves regenerated after spinal cord injury". The Los Angeles Times. August 13, 2010.
  27. ↑ Liu K, Lu Y, Lee JK, Samara R, Willenberg R, Sears-Kraxberger I, et al. (September 2010). "PTEN deletion enhances the regenerative ability of adult corticospinal neurons". Nature Neuroscience. 13 (9): 1075–1081. doi:10.1038/nn.2603. PMC   2928871 . PMID   20694004.
  28. ↑ Leibinger M, Hilla AM, Andreadaki A, Fischer D (2019). "GSK3-CRMP2 signaling mediates axonal regeneration induced by Pten knockout". Communications Biology. 2: 318. doi:10.1038/s42003-019-0524-1. PMC   6707209 . PMID   31453382.
  29. ↑ Walker CL, Walker MJ, Liu NK, Risberg EC, Gao X, Chen J, Xu XM (2012). "Systemic bisperoxovanadium activates Akt/mTOR, reduces autophagy, and enhances recovery following cervical spinal cord injury". PLOS ONE. 7 (1): e30012. Bibcode:2012PLoSO...730012W. doi: 10.1371/journal.pone.0030012 . PMC   3254642 . PMID   22253859.
  30. ↑ Rozenberg K, Smirin P, Sampson SR, Rosenzweig T (August 2014). "Insulin-sensitizing and insulin-mimetic activities of Sarcopoterium spinosum extract". Journal of Ethnopharmacology. 155 (1): 362–372. doi:10.1016/j.jep.2014.05.030. PMID   24882728.
  31. 1 2 Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, et al. (March 1997). "PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer". Science. 275 (5308): 1943–1947. doi:10.1126/science.275.5308.1943. PMID   9072974. S2CID   23093929.
  32. 1 2 Miller SJ, Lou DY, Seldin DC, Lane WS, Neel BG (September 2002). "Direct identification of PTEN phosphorylation sites". FEBS Letters. 528 (1–3): 145–153. doi: 10.1016/S0014-5793(02)03274-X . PMID   12297295. S2CID   1093672.
  33. ↑ Wu Y, Dowbenko D, Spencer S, Laura R, Lee J, Gu Q, Lasky LA (July 2000). "Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of MAGI3, a novel membrane-associated guanylate kinase". The Journal of Biological Chemistry. 275 (28): 21477–21485. doi: 10.1074/jbc.M909741199 . PMID   10748157.
  34. ↑ Yu Z, Fotouhi-Ardakani N, Wu L, Maoui M, Wang S, Banville D, Shen SH (October 2002). "PTEN associates with the vault particles in HeLa cells". The Journal of Biological Chemistry. 277 (43): 40247–40252. doi: 10.1074/jbc.M207608200 . PMID   12177006.
  35. ↑ Wang X, Shi Y, Wang J, Huang G, Jiang X (September 2008). "Crucial role of the C-terminus of PTEN in antagonizing NEDD4-1-mediated PTEN ubiquitination and degradation". The Biochemical Journal. 414 (2): 221–229. doi:10.1042/BJ20080674. PMID   18498243.
  36. ↑ Lin HK, Hu YC, Lee DK, Chang C (October 2004). "Regulation of androgen receptor signaling by PTEN (phosphatase and tensin homolog deleted on chromosome 10) tumor suppressor through distinct mechanisms in prostate cancer cells". Molecular Endocrinology. 18 (10): 2409–2423. doi: 10.1210/me.2004-0117 . PMID   15205473.
  37. ↑ Freeman DJ, Li AG, Wei G, Li HH, Kertesz N, Lesche R, et al. (February 2003). "PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms". Cancer Cell. 3 (2): 117–130. doi: 10.1016/S1535-6108(03)00021-7 . PMID   12620407.
  38. ↑ Tamura M, Gu J, Danen EH, Takino T, Miyamoto S, Yamada KM (July 1999). "PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidylinositol 3-kinase/Akt cell survival pathway". The Journal of Biological Chemistry. 274 (29): 20693–20703. doi: 10.1074/jbc.274.29.20693 . PMID   10400703.
  39. ↑ Haier J, Nicolson GL (February 2002). "PTEN regulates tumor cell adhesion of colon carcinoma cells under dynamic conditions of fluid flow". Oncogene. 21 (9): 1450–1460. doi: 10.1038/sj.onc.1205213 . PMID   11857088.

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