Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Molecular Medicine
  4. Volume 24, Issue 12
  5. Article
Volume 24, Issue 12
  • ISSN: 1566-5240
  • E-ISSN:

Abstract

Objectives

Polypyrimidine tract binding protein is a 57-Kda protein located in the perinucleolar compartment where it binds RNA and regulates several biological functions through the regulation of RNA splicing. Numerous research articles have been published that address the cellular network and functions of PTB and its isoforms in various disease states.

Methodology

Through an extensive PubMed search, we attempt to summarize the relevant research into this biomolecule.

Results

Besides its roles in embryonic development, neuronal cell growth, RNA metabolism, apoptosis, and hematopoiesis, PTB can affect cancer growth several metabolic, proliferative, and structural mechanisms. PTB overexpression has been documented in several cancers where it plays a role as a novel prognostic factor.

Conclusion

The diverse carcinogenic effect opens an argument into its potential role in inhibitory targeted therapy.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmm/10.2174/0115665240251370231017053236
2024-01-01
2024-10-12

  • From This Site

    /content/journals/cmm/10.2174/0115665240251370231017053236
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. KoppK. HuangS. Perinucleolar compartment and transformation.J. Cell. Biochem.200595221722510.1002/jcb.20403 15770648
     [Google Scholar]
  2. PollockC. HuangS. The perinucleolar compartment.J. Cell. Biochem.2009107218919310.1002/jcb.22107 19288520
     [Google Scholar]
  3. WenY. WangC. HuangS. The perinucleolar compartment associates with malignancy.Front. Biol.20138436937610.1007/s11515‑013‑1265‑z 24348523
     [Google Scholar]
  4. SawickaK. BushellM. SpriggsK.A. WillisA.E. Polypyrimidine-tract-binding protein: A multifunctional RNA-binding protein.Biochem. Soc. Trans.200836464164710.1042/BST0360641 18631133
     [Google Scholar]
  5. AuweterS.D. AllainF.H.T. Structure-function relationships of the polypyrimidine tract binding protein.Cell. Mol. Life Sci.200865451652710.1007/s00018‑007‑7378‑2 17975705
     [Google Scholar]
  6. RomanelliM. DianiE. LievensP. New insights into functional roles of the polypyrimidine tract-binding protein.Int. J. Mol. Sci.20131411229062293210.3390/ijms141122906 24264039
     [Google Scholar]
  7. WangC. NortonJ.T. GhoshS. Polypyrimidine tract-binding protein (PTB) differentially affects malignancy in a cell line-dependent manner.J. Biol. Chem.200828329202772028710.1074/jbc.M803682200 18499661
     [Google Scholar]
  8. PinaJ.M. ReynagaJ.M. TruongA.A.M. KeppetipolaN.M. Post-translational modifications in polypyrimidine tract binding proteins PTBP1 and PTBP2.Biochemistry201857263873388210.1021/acs.biochem.8b00256 29851470
     [Google Scholar]
  9. DaiS. WangC. ZhangC. PTB: Not just a polypyrimidine tract‐binding protein.J. Cell. Physiol.202223752357237310.1002/jcp.30716 35288937
     [Google Scholar]
  10. SpellmanR. RideauA. MatlinA. Regulation of alternative splicing by PTB and associated factors.Biochem. Soc. Trans.200533345746010.1042/BST0330457 15916540
     [Google Scholar]
  11. Arake de TaccaL.M. Pulos-HolmesM.C. FloorS.N. CateJ.H.D. PTBP1 mRNA isoforms and regulation of their translation.RNA201925101324133610.1261/rna.070193.118 31263002
     [Google Scholar]
  12. MéreauA. AnquetilV. LerivrayH. A posttranscriptional mechanism that controls Ptbp1 abundance in the Xenopus epidermis.Mol. Cell. Biol.201535475876810.1128/MCB.01040‑14 25512611
     [Google Scholar]
  13. CoelhoM.B. AttigJ. BelloraN. Nuclear matrix protein Matrin3 regulates alternative splicing and forms overlapping regulatory networks with PTB.EMBO J.201534565366810.15252/embj.201489852 25599992
     [Google Scholar]
  14. LucoR.F. PanQ. TominagaK. BlencoweB.J. Pereira-SmithO.M. MisteliT. Regulation of alternative splicing by histone modifications.Science20103275968996100010.1126/science.1184208 20133523
     [Google Scholar]
  15. SchorrA.L. MangoneM. miRNA-based regulation of alternative RNA splicing in metazoans.Int. J. Mol. Sci.202122211161810.3390/ijms222111618 34769047
     [Google Scholar]
  16. GeZ. QuekB.L. BeemonK.L. HoggJ.R. Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway.eLife20165e1115510.7554/eLife.11155 26744779
     [Google Scholar]
  17. FritzS.E. RanganathanS. WangC.D. HoggJ.R. The RNA-binding protein PTBP1 promotes ATPase-dependent dissociation of the RNA helicase UPF1 to protect transcripts from nonsense-mediated mRNA decay.J. Biol. Chem.202029533116131162510.1074/jbc.RA120.013824 32571872
     [Google Scholar]
  18. ShibayamaM. OhnoS. OsakaT. Polypyrimidine tract-binding protein is essential for early mouse development and embryonic stem cell proliferation.FEBS J.2009276226658666810.1111/j.1742‑4658.2009.07380.x 19843185
     [Google Scholar]
  19. SuckaleJ. WendlingO. MasjkurJ. PTBP1 is required for embryonic development before gastrulation.PLoS One201162e1699210.1371/journal.pone.0016992 21423341
     [Google Scholar]
  20. SenooM. TakijiriT. YoshidaN. OzawaM. IkawaM. PTBP1 contributes to spermatogenesis through regulation of proliferation in spermatogonia.J. Reprod. Dev.2019651374610.1262/jrd.2018‑109 30416150
     [Google Scholar]
  21. DengY. XuX. MengF. PRP8-induced CircMaml2 facilitates the healing of the intestinal mucosa via recruiting PTBP1 and regulating sec62.Cells20221121346010.3390/cells11213460 36359856
     [Google Scholar]
  22. CuiJ. PlaczekW.J. PTBP1 enhances miR-101-guided AGO2 targeting to MCL1 and promotes miR-101-induced apoptosis.Cell Death Dis.20189555210.1038/s41419‑018‑0551‑8 29748555
     [Google Scholar]
  23. JuanW.C. RocaX. OngS.T. Identification of cis-acting elements and splicing factors involved in the regulation of BIM Pre-mRNA splicing.PLoS One201494e9521010.1371/journal.pone.0095210 24743263
     [Google Scholar]
  24. La PortaJ. Matus-NicodemosR. Valentín-AcevedoA. CoveyL.R. The RNA-binding protein, polypyrimidine tract-binding protein 1 (PTBP1) is a key regulator of CD4 T cell activation.PLoS One2016118e015870810.1371/journal.pone.0158708 27513449
     [Google Scholar]
  25. DominguesR.G. Lago-BaldaiaI. Pereira-CastroI. CD5 expression is regulated during human T-cell activation by alternative polyadenylation, PTBP1, and miR-204.Eur. J. Immunol.20164661490150310.1002/eji.201545663 27005442
     [Google Scholar]
  26. TangS.J. LuoS. HoJ.X.J. LyP.T. GohE. RocaX. Characterization of the regulation of CD46 RNA alternative splicing.J. Biol. Chem.201629127143111432310.1074/jbc.M115.710350 27226545
     [Google Scholar]
  27. SasanumaH. OzawaM. YoshidaN. RNA-binding protein Ptbp1 is essential for BCR-mediated antibody production.Int. Immunol.201931315716610.1093/intimm/dxy077 30476084
     [Google Scholar]
  28. GengG. XuC. PengN. PTBP1 is necessary for dendritic cells to regulate T‐cell homeostasis and antitumour immunity.Immunology20211631748510.1111/imm.13304 33421118
     [Google Scholar]
  29. ZhuW. ZhouB. RongL. Roles of PTBP1 in alternative splicing, glycolysis, and oncogensis.J. Zhejiang Univ. Sci. B202021212213610.1631/jzus.B1900422 32115910
     [Google Scholar]
  30. WangX. LiY. FanY. YuX. MaoX. JinF. PTBP1 promotes the growth of breast cancer cells through the PTEN/Akt pathway and autophagy.J. Cell. Physiol.2018233118930893910.1002/jcp.26823 29856478
     [Google Scholar]
  31. HeX. YuanC. YangJ. Regulation and functional significance of CDC42 alternative splicing in ovarian cancer.Oncotarget2015630296512966310.18632/oncotarget.4865 26336992
     [Google Scholar]
  32. FuX. XieF. GongF. Suppression of PTBP1 signaling is responsible for mesenchymal stem cell induced invasion of low malignancy cancer cells.Biochim. Biophys. Acta Mol. Cell Res.20181865111552156510.1016/j.bbamcr.2018.08.002 30327198
     [Google Scholar]
  33. HollanderD. DonyoM. AtiasN. A network-based analysis of colon cancer splicing changes reveals a tumorigenesis-favoring regulatory pathway emanating from ELK1.Genome Res.201626454155310.1101/gr.193169.115 26860615
     [Google Scholar]
  34. TaniguchiK. UchiyamaK. AkaoY. PTBP1 ‐targeting microRNAs regulate cancer‐specific energy metabolism through the modulation of PKM1/M2 splicing.Cancer Sci.20211121415010.1111/cas.14694 33070451
     [Google Scholar]
  35. KuranagaY. SugitoN. ShinoharaH. SRSF3, a splicer of the PKM gene, regulates cell growth and maintenance of cancer-specific energy metabolism in colon cancer cells.Int. J. Mol. Sci.20181910301210.3390/ijms19103012 30279379
     [Google Scholar]
  36. CuiJ. PlaczekW.J. PTBP1 modulation of MCL1 expression regulates cellular apoptosis induced by antitubulin chemotherapeutics.Cell Death Differ.201623101681169010.1038/cdd.2016.60 27367564
     [Google Scholar]
  37. LiX. HanF. LiuW. ShiX. PTBP1 promotes tumorigenesis by regulating apoptosis and cell cycle in colon cancer.Bull. Cancer2018105121193120110.1016/j.bulcan.2018.08.013 30309622
     [Google Scholar]
  38. JoY.K. RohS.A. LeeH. Polypyrimidine tract-binding protein 1-mediated down-regulation of ATG10 facilitates metastasis of colorectal cancer cells.Cancer Lett.2017385212710.1016/j.canlet.2016.11.002 27836735
     [Google Scholar]
  39. LiS. ShenL. HuangL. PTBP1 enhances exon11a skipping in Mena pre-mRNA to promote migration and invasion in lung carcinoma cells.Biochim. Biophys. Acta. Gene Regul. Mech.20191862885886910.1016/j.bbagrm.2019.04.006 31075540
     [Google Scholar]
  40. ChoC.Y. ChungS.Y. LinS. PTBP1-mediated regulation of AXL mRNA stability plays a role in lung tumorigenesis.Sci. Rep.2019911692210.1038/s41598‑019‑53097‑2 31729427
     [Google Scholar]
  41. MinamiK. TaniguchiK. SugitoN. MiR-145 negatively regulates Warburg effect by silencing KLF4 and PTBP1 in bladder cancer cells.Oncotarget2017820330643307710.18632/oncotarget.16524 28380435
     [Google Scholar]
  42. SugiyamaT. TaniguchiK. MatsuhashiN. MiR‐133b inhibits growth of human gastric cancer cells by silencing pyruvate kinase muscle‐splicer polypyrimidine tract‐binding protein 1.Cancer Sci.2016107121767177510.1111/cas.13091 27696637
     [Google Scholar]
  43. FerrareseR. HarshG.R.IV YadavA.K. Lineage-specific splicing of a brain-enriched alternative exon promotes glioblastoma progression.J. Clin. Invest.201412472861287610.1172/JCI68836 24865424
     [Google Scholar]
  44. TaniguchiK. SugitoN. KumazakiM. MicroRNA-124 inhibits cancer cell growth through PTB1/PKM1/PKM2 feedback cascade in colorectal cancer.Cancer Lett.20153631172710.1016/j.canlet.2015.03.026 25818238
     [Google Scholar]
  45. ZhangX. ZhouY. ChenS. LiW. ChenW. GuW. LncRNA MACC1-AS1 sponges multiple miRNAs and RNA-binding protein PTBP1.Oncogenesis20198127310.1038/s41389‑019‑0182‑7 31822653
     [Google Scholar]
  46. HuanL. GuoT. WuY. Hypoxia induced LUCAT1/PTBP1 axis modulates cancer cell viability and chemotherapy response.Mol. Cancer20201911110.1186/s12943‑019‑1122‑z 31964396
     [Google Scholar]
  47. ShengJ. HeX. YuW. p53-targeted lncRNA ST7-AS1 acts as a tumour suppressor by interacting with PTBP1 to suppress the Wnt/β-catenin signalling pathway in glioma.Cancer Lett.2021503546810.1016/j.canlet.2020.12.039 33476649
     [Google Scholar]
  48. ChenJ. WuY. LuoX. Circular RNA circRHOBTB3 represses metastasis by regulating the HuR-mediated mRNA stability of PTBP1 in colorectal cancer.Theranostics202111157507752610.7150/thno.59546 34158864
     [Google Scholar]
  49. WangS. ZhangY. CaiQ. Circular RNA FOXP1 promotes tumor progression and Warburg effect in gallbladder cancer by regulating PKLR expression.Mol. Cancer201918114510.1186/s12943‑019‑1078‑z 31623628
     [Google Scholar]
  50. SunY.M. WangW.T. ZengZ.C. circMYBL2, a circRNA from MYBL2, regulates FLT3 translation by recruiting PTBP1 to promote FLT3-ITD AML progression.Blood2019134181533154610.1182/blood.2019000802 31387917
     [Google Scholar]
  51. CenY. ZhuT. ZhangY. hsa_circ_0005358 suppresses cervical cancer metastasis by interacting with PTBP1 protein to destabilize CDCP1 mRNA.Mol. Ther. Nucleic Acids20222722724010.1016/j.omtn.2021.11.020 34976440
     [Google Scholar]
  52. WangC. PolitzJ.C. PedersonT. HuangS. RNA polymerase III transcripts and the PTB protein are essential for the integrity of the perinucleolar compartment.Mol. Biol. Cell20031462425243510.1091/mbc.e02‑12‑0818 12808040
     [Google Scholar]
  53. SlusarczykA. KamathR. WangC. Structure and function of the perinucleolar compartment in cancer cells.Cold Spring Harb. Symp. Quant. Biol.201075059960510.1101/sqb.2010.75.026 21289045
     [Google Scholar]
  54. HallM.P. HuangS. BlackD.L. Differentiation-induced colocalization of the KH-type splicing regulatory protein with polypyrimidine tract binding protein and the c-src pre-mRNA.Mol. Biol. Cell200415277478610.1091/mbc.e03‑09‑0692 14657238
     [Google Scholar]
  55. LiuW. ChouC.F. LiuS. KSRP modulates melanoma growth and efficacy of vemurafenib.Biochim. Biophys. Acta. Gene Regul. Mech.20191862875977010.1016/j.bbagrm.2019.06.005 31269460
     [Google Scholar]
  56. HüttelmaierS. IllenbergerS. GroshevaI. RüdigerM. SingerR.H. JockuschB.M. Raver1, a dual compartment protein, is a ligand for PTB/hnRNPI and microfilament attachment proteins.J. Cell Biol.2001155577578610.1083/jcb.200105044 11724819
     [Google Scholar]
  57. SpellmanR. LlorianM. SmithC.W.J. Crossregulation and functional redundancy between the splicing regulator PTB and its paralogs nPTB and ROD1.Mol. Cell200727342043410.1016/j.molcel.2007.06.016 17679092
     [Google Scholar]
  58. SlusarczykA. HuangS. The perinucleolar compartment (PNC): Detection by immunohistochemistry.Methods Mol. Biol.200846316116710.1007/978‑1‑59745‑406‑3_11 18951167
     [Google Scholar]
  59. BaiH. ChenB. Abnormal PTBP1 expression sustains the disease progression of multiple myeloma.Dis. Markers2020202011010.1155/2020/4013658 32655719
     [Google Scholar]
  60. ChengC. DingQ. ZhangZ. PTBP1 modulates osteosarcoma chemoresistance to cisplatin by regulating the expression of the copper transporter SLC31A1.J. Cell. Mol. Med.20202495274528910.1111/jcmm.15183 32207235
     [Google Scholar]
  61. KangH. HeoS. ShinJ.J. A miR‐194/PTBP1/CCND3 axis regulates tumor growth in human hepatocellular carcinoma.J. Pathol.2019249339540810.1002/path.5325 31301177
     [Google Scholar]
  62. ChenC. ShangA. GaoY. PTBPs: An immunomodulatory-related prognostic biomarker in pan-cancer.Front. Mol. Biosci.2022996845810.3389/fmolb.2022.968458 36203873
     [Google Scholar]
  63. NandagopalanS.R. AgatheeswaranS. VadlamudiY. PTBP2 exon 10 inclusion is associated with the progression of CML and it is BCR-ABL1 dependent.Int. J. Biochem. Cell Biol.2019109697510.1016/j.biocel.2019.01.018 30726713
     [Google Scholar]
  64. AgatheeswaranS. SinghS. BiswasS. BiswasG. Chandra PattnayakN. ChakrabortyS. BCR-ABL mediated repression of miR-223 results in the activation of MEF2C and PTBP2 in chronic myeloid leukemia.Leukemia20132771578158010.1038/leu.2012.339 23174904
     [Google Scholar]
  65. XieC. LongF. LiL. PTBP3 modulates P53 expression and promotes colorectal cancer cell proliferation by maintaining UBE4A mRNA stability.Cell Death Dis.202213212810.1038/s41419‑022‑04564‑8 35136024
     [Google Scholar]
  66. HouP. ChenF. YongH. PTBP3 contributes to colorectal cancer growth and metastasis via translational activation of HIF-1α.J. Exp. Clin. Cancer Res.201938130110.1186/s13046‑019‑1312‑y 31291975
     [Google Scholar]
  67. MaJ. WengL. JiaY. PTBP3 promotes malignancy and hypoxia‐induced chemoresistance in pancreatic cancer cells by ATG12 up‐regulation.J. Cell. Mol. Med.20202452917293010.1111/jcmm.14896 31989778
     [Google Scholar]
  68. LiangX. ChenW. ShiH. PTBP3 contributes to the metastasis of gastric cancer by mediating CAV1 alternative splicing.Cell Death Dis.20189556910.1038/s41419‑018‑0608‑8 29752441
     [Google Scholar]
  69. ChenB. ChenW. MuX. PTBP3 induced inhibition of differentiation of gastric cancer cells through alternative splicing of Id1.Front. Oncol.202010147710.3389/fonc.2020.01477 32974175
     [Google Scholar]
  70. DongC. WuK. GuS. WangW. XieS. ZhouY. PTBP3 mediates TGF-β-induced EMT and metastasis of lung adenocarcinoma.Cell Cycle202221131406142110.1080/15384101.2022.2052530 35323096
     [Google Scholar]
  71. ChenY. JiY. LiuS. LiuY. FengW. JinL. PTBP3 regulates proliferation of lung squamous cell carcinoma cells via CDC25A‐mediated cell cycle progression.Cancer Cell Int.20222211910.1186/s12935‑022‑02448‑7 35016691
     [Google Scholar]
  72. HouP. LiL. ChenF. PTBP3-mediated regulation of ZEB1 mRNA stability promotes epithelial–mesenchymal transition in breast cancer.Cancer Res.201878238739810.1158/0008‑5472.CAN‑17‑0883 29187406
     [Google Scholar]
  73. ZhouY. ZouH. WuE. Overexpression of ROD1 inhibits invasion of breast cancer cells by suppressing the translocation of β catenin into the nucleus.Oncol. Lett.20181622645265310.3892/ol.2018.8917 30013660
     [Google Scholar]
/content/journals/cmm/10.2174/0115665240251370231017053236
Loading
Polypyrimidine Tract Binding Protein: A Universal Player in Cancer Development
Current Molecular Medicine 24, 1450 (2024); https://doi.org/10.2174/0115665240251370231017053236
/content/journals/cmm/10.2174/0115665240251370231017053236
/content/journals/cmm/10.2174/0115665240251370231017053236
Loading

Data & Media loading...

  • Article Type: Review Article
Keyword(s): apoptosis; cancer; hematopoiesis; PNC; Polypyrimidine tract binding protein; RNA splicing

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test