Home LiteratureArticle Details
PMID: 15684381 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Polypyrimidine tract-binding protein enhances the internal ribosomal entry site-dependent translation of p27Kip1 mRNA and modulates transition from G1 to S phase.

Molecular and cellular biology ·Vol. 25 ·No. 4 ·2005-02-00 ·Pages 1283-97

Cho S, Kim JH, Back SH, Jang SK

Abstract

The p27(Kip1) protein plays a critical role in the regulation of cell proliferation through the inhibition of cyclin-dependent kinase activity. Translation of p27(Kip1) is directed by an internal ribosomal entry site (IRES) in the 5' nontranslated region of p27(Kip1) mRNA. Here, we report that polypyrimidine tract-binding protein (PTB) specifically enhances the IRES activity of p27(Kip1) mRNA through an interaction with the IRES element. We found that addition of PTB to an in vitro translation system and overexpression of PTB in 293T cells augmented the IRES activity of p27(Kip1) mRNA but that knockdown of PTB by introduction of PTB-specific small interfering RNAs (siRNAs) diminished the IRES activity of p27(Kip1) mRNA. Moreover, the G(1) phase in the cell cycle (which is maintained in part by p27(Kip1)) was shortened in cells depleted of PTB by siRNA knockdown. 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced differentiation in HL60 cells was used to examine PTB-induced modulation of p27(Kip1) protein synthesis during differentiation. The IRES activity of p27(Kip1) mRNA in HL60 cells was increased by TPA treatment (with a concomitant increase in PTB protein levels), but the levels of p27(Kip1) mRNA remained unchanged. Together, these data suggest that PTB modulates cell cycle and differentiation, at least in part, by enhancing the IRES activity of p27(Kip1) mRNA.

MeSH Terms
Cell Cycle Proteins/metabolism Cell Differentiation/drug effects,physiology Cells, Cultured Cyclin-Dependent Kinase Inhibitor p27 G1 Phase/drug effects,physiology HL-60 Cells HeLa Cells Humans Peptide Chain Initiation, Translational/drug effects,physiology Phorbol Esters/pharmacology Polypyrimidine Tract-Binding Protein/metabolism RNA, Small Interfering/metabolism Ribosomes/metabolism S Phase/drug effects,physiology Tumor Suppressor Proteins/metabolism
Chemicals
Cell Cycle Proteins Phorbol Esters RNA, Small Interfering Tumor Suppressor Proteins Polypyrimidine Tract-Binding Protein Cyclin-Dependent Kinase Inhibitor p27
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Cho Sungchan
PBC, Division of Molecular and Life Science, Pohang University of Science and Technology, San 31, Hyoja Dong, Pohang, Kyungbuk 790-784, South Korea. sungkey@postech.ac.kr
Kim Jong Heon
Back Sung Hoon
Jang Sung Key
References (50)
50 references, click to expand
  1. Sp1 and NF-Y synergistically mediate the effect of vitamin D(3) in the p27(Kip1) gene promoter that lacks vitamin D response elements.
    J Biol Chem. 1999 Nov 5;274(45):32309-17 PMID: 10542271
  2. Changes in cyclin-dependent kinase 2 and p27kip1 accompany glial cell differentiation of central glia-4 cells.
    J Biol Chem. 1997 Jan 3;272(1):442-7 PMID: 8995281
  3. Overexpression of p21Cip1 or p27Kip1 in the promyelocytic leukemia cell line HL60 accelerates its lineage-specific differentiation.
    Anticancer Res. 1999 Nov-Dec;19(6B):4935-45 PMID: 10697493
  4. Protein-protein interaction among hnRNPs shuttling between nucleus and cytoplasm.
    J Mol Biol. 2000 May 5;298(3):395-405 PMID: 10772858
  5. A segment of the 5' nontranslated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation.
    J Virol. 1988 Aug;62(8):2636-43 PMID: 2839690
  6. A factor that specifically binds to the 5'-untranslated region of encephalomyocarditis virus RNA.
    FEBS Lett. 1990 Feb 26;261(2):237-40 PMID: 2155820
  7. Cap-independent translation of encephalomyocarditis virus RNA: structural elements of the internal ribosomal entry site and involvement of a cellular 57-kD RNA-binding protein.
    Genes Dev. 1990 Sep;4(9):1560-72 PMID: 2174810
  8. Accumulation of the cyclin-dependent kinase inhibitor p27/Kip1 and the timing of oligodendrocyte differentiation.
    EMBO J. 1997 Jan 15;16(2):306-17 PMID: 9029151
  9. Enhanced ribosomal association of p27(Kip1) mRNA is a mechanism contributing to accumulation during growth arrest.
    J Biol Chem. 1997 Mar 14;272(11):7093-8 PMID: 9054402
  10. PDGF2/c-sis mRNA leader contains a differentiation-linked internal ribosomal entry site (D-IRES).
    J Biol Chem. 1997 Apr 4;272(14):9356-62 PMID: 9083072
  11. Oligodendrocyte precursor differentiation is perturbed in the absence of the cyclin-dependent kinase inhibitor p27Kip1.
    Genes Dev. 1997 Sep 15;11(18):2335-46 PMID: 9308962
  12. Multiple RRMs contribute to RNA binding specificity and affinity for polypyrimidine tract binding protein.
    Biochemistry. 1997 Sep 30;36(39):11881-90 PMID: 9305981
  13. Cyclin-dependent kinases: engines, clocks, and microprocessors.
    Annu Rev Cell Dev Biol. 1997;13:261-91 PMID: 9442875
  14. DNA methylation regulates p27kip1 expression in rodent pituitary cell lines.
    Am J Pathol. 1998 Nov;153(5):1475-82 PMID: 9811339
  15. New insights into the tumor suppression function of P27(kip1)
    Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15158-60 PMID: 9860936
  16. Cell-free degradation of p27(kip1), a G1 cyclin-dependent kinase inhibitor, is dependent on CDK2 activity and the proteasome.
    Mol Cell Biol. 1999 Feb;19(2):1190-201 PMID: 9891053
  17. p27kip1: a multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers.
    Am J Pathol. 1999 Feb;154(2):313-23 PMID: 10027389
  18. Translational control of specific genes during differentiation of HL-60 cells.
    J Biol Chem. 1999 May 14;274(20):14295-305 PMID: 10318851
  19. CDK inhibitors: positive and negative regulators of G1-phase progression.
    Genes Dev. 1999 Jun 15;13(12):1501-12 PMID: 10385618
  20. Differentiation-induced internal translation of c-sis mRNA: analysis of the cis elements and their differentiation-linked binding to the hnRNP C protein.
    Mol Cell Biol. 1999 Aug;19(8):5429-40 PMID: 10409733
  21. The cell cycle regulator p27kip1 contributes to growth and differentiation of osteoblasts.
    Cancer Res. 1999 Aug 1;59(15):3705-11 PMID: 10446985
  22. A U-rich element in the 5' untranslated region is necessary for the translation of p27 mRNA.
    Mol Cell Biol. 2000 Aug;20(16):5947-59 PMID: 10913178
  23. c-myc Internal ribosome entry site activity is developmentally controlled and subjected to a strong translational repression in adult transgenic mice.
    Mol Cell Biol. 2001 Mar;21(5):1833-40 PMID: 11238920
  24. Control of cyclin-dependent kinase inhibitor p27 expression by cap-independent translation.
    Mol Cell Biol. 2001 Aug;21(15):4960-7 PMID: 11438653
  25. Translation of polioviral mRNA is inhibited by cleavage of polypyrimidine tract-binding proteins executed by polioviral 3C(pro).
    J Virol. 2002 Mar;76(5):2529-42 PMID: 11836431
  26. Role of PTB-like protein, a neuronal RNA-binding protein, during the differentiation of PC12 cells.
    J Biochem. 2002 Jun;131(6):861-8 PMID: 12038983
  27. ELAV/Hu proteins inhibit p27 translation via an IRES element in the p27 5'UTR.
    Genes Dev. 2002 Dec 1;16(23):3087-99 PMID: 12464637
  28. Heterogeneous nuclear ribonucleoprotein C modulates translation of c-myc mRNA in a cell cycle phase-dependent manner.
    Mol Cell Biol. 2003 Jan;23(2):708-20 PMID: 12509468
  29. The Apaf-1 internal ribosome entry segment attains the correct structural conformation for function via interactions with PTB and unr.
    Mol Cell. 2003 Mar;11(3):757-71 PMID: 12667457
  30. Drosophila polypyrimidine-tract binding protein (PTB) functions specifically in the male germline.
    EMBO J. 2003 Jun 16;22(12):2924-33 PMID: 12805208
  31. Identification of cellular proteins enhancing activities of internal ribosomal entry sites by competition with oligodeoxynucleotides.
    Nucleic Acids Res. 2004;32(4):1308-17 PMID: 14981151
  32. The Apc5 subunit of the anaphase-promoting complex/cyclosome interacts with poly(A) binding protein and represses internal ribosome entry site-mediated translation.
    Mol Cell Biol. 2004 May;24(9):3577-87 PMID: 15082755
  33. A cellular RNA-binding protein enhances internal ribosomal entry site-dependent translation through an interaction downstream of the hepatitis C virus polyprotein initiation codon.
    Mol Cell Biol. 2004 Sep;24(18):7878-90 PMID: 15340051
  34. Cap-independent translation of poliovirus mRNA is conferred by sequence elements within the 5' noncoding region.
    Mol Cell Biol. 1988 Mar;8(3):1103-12 PMID: 2835660
  35. Characterization and molecular cloning of polypyrimidine tract-binding protein: a component of a complex necessary for pre-mRNA splicing.
    Genes Dev. 1991 Jul;5(7):1237-51 PMID: 1906036
  36. hnRNP I, the polypyrimidine tract-binding protein: distinct nuclear localization and association with hnRNAs.
    Nucleic Acids Res. 1992 Jul 25;20(14):3671-8 PMID: 1641332
  37. Cyclin-dependent regulation of G1 in mammalian fibroblasts.
    Science. 1993 Mar 26;259(5103):1908-12 PMID: 8384376
  38. p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest.
    Genes Dev. 1994 Jan;8(1):9-22 PMID: 8288131
  39. Acceleration of the G1/S phase transition by expression of cyclins D1 and E with an inducible system.
    Mol Cell Biol. 1994 Mar;14(3):1669-79 PMID: 8114703
  40. Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals.
    Cell. 1994 Jul 15;78(1):59-66 PMID: 8033212
  41. Cdk inhibitors: on the threshold of checkpoints and development.
    Curr Opin Cell Biol. 1994 Dec;6(6):847-52 PMID: 7880532
  42. Inhibitors of mammalian G1 cyclin-dependent kinases.
    Genes Dev. 1995 May 15;9(10):1149-63 PMID: 7758941
  43. Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27.
    Science. 1995 Aug 4;269(5224):682-5 PMID: 7624798
  44. Inhibition of cyclin-dependent kinase activity triggers neuronal differentiation of mouse neuroblastoma cells.
    J Cell Biol. 1995 Oct;131(1):227-34 PMID: 7559779
  45. Direct evidence that polypyrimidine tract binding protein (PTB) is essential for internal initiation of translation of encephalomyocarditis virus RNA.
    RNA. 1995 Nov;1(9):924-38 PMID: 8548657
  46. Dependence of cyclin E-CDK2 kinase activity on cell anchorage.
    Science. 1996 Jan 26;271(5248):499-502 PMID: 8560263
  47. Translational control of p27Kip1 accumulation during the cell cycle.
    Science. 1996 Mar 29;271(5257):1861-4 PMID: 8596954
  48. Repression of p27kip1 synthesis by platelet-derived growth factor in BALB/c 3T3 cells.
    Mol Cell Biol. 1996 Aug;16(8):4327-36 PMID: 8754833
  49. Signal sequences that target nuclear import and nuclear export of pre-mRNA-binding proteins.
    Cold Spring Harb Symp Quant Biol. 1995;60:663-8 PMID: 8824440
  50. Monocytically differentiating HL60 cells proliferate rapidly before they mature.
    Exp Cell Res. 1999 Dec 15;253(2):511-8 PMID: 10585274
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.25.4.1283-1297.2005
Email
sungkey@postech.ac.kr
Published
2005-02-00
Pages
1283-97
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC548013
Subset
IM
Grants
NIEHS NIH HHS · 27305C0011 · United States
NIEHS NIH HHS · 27307C0011 · United States
NIEHS NIH HHS · 27398C0011 · United States
External Links
PubMed source DOI: 10.1128/MCB.25.4.1283-1297.2005 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2