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PMID: 12773549 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The Sp1 family of transcription factors is involved in p27(Kip1)-mediated activation of myelin basic protein gene expression.

Molecular and cellular biology ·Vol. 23 ·No. 12 ·2003-06-00 ·Pages 4035-45

Wei Q, Miskimins WK, Miskimins R

Abstract

p27(Kip1) levels increase in many cells as they leave the cell cycle and begin to differentiate. The increase in p27(Kip1) levels generally precedes the expression of differentiation-specific genes. Previous studies from our laboratory showed that the overexpression of p27(Kip1) enhances myelin basic protein (MBP) promoter activity. This activation is specific to p27(Kip1). Additionally, inhibition of cyclin-dependent kinase activity alone is not sufficient to increase MBP expression. In this study, we focused on understanding how p27(Kip1) can activate gene transcription by using the MBP gene in oligodendrocytes as a model. We show that the enhancement of MBP promoter activity by p27(Kip1) is mediated by a proximal region of the MBP promoter that contains a conserved GC box binding sequence. This sequence binds transcription factors Sp1 and Sp3. Increased expression of p27(Kip1) increases the level of Sp1 promoter binding to the GC box but does not change the level of Sp3 binding. The binding of Sp1 to this element activates the MBP promoter. p27(Kip1) leads to increased Sp1 binding through a decrease in Sp1 protein turnover. Enhancement of MBP promoter activity by an increase in the level of p27(Kip1) involves a novel mechanism that is mediated through the stabilization and binding of transcription factor Sp1.

MeSH Terms
Animals Cell Cycle Proteins/metabolism Cell Differentiation Cells, Cultured Cyclin-Dependent Kinase Inhibitor p27 Electrophoresis, Polyacrylamide Gel Gene Expression Regulation Luciferases/metabolism Mutagenesis, Site-Directed Mutation Myelin Basic Protein/metabolism Oligodendroglia/metabolism Plasmids/metabolism Precipitin Tests Promoter Regions, Genetic Protein Binding Rats Sp1 Transcription Factor/metabolism Time Factors Transcription, Genetic Transcriptional Activation Transfection Tumor Suppressor Proteins/metabolism
Chemicals
Cdkn1b protein, rat Cell Cycle Proteins Myelin Basic Protein Sp1 Transcription Factor Tumor Suppressor Proteins Cyclin-Dependent Kinase Inhibitor p27 Luciferases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Wei Qiou
Division of Basic Biomedical Sciences, School of Medicine, University of South Dakota, Vermillion, South Dakota 57069, USA.
Miskimins W Keith
Miskimins Robin
References (40)
40 references, click to expand
  1. Expression and role of p27(kip1) in neuronal differentiation of embryonal carcinoma cells.
    Brain Res Mol Brain Res. 2000 May 5;77(2):209-21 PMID: 10837916
  2. Human Sug1/p45 is involved in the proteasome-dependent degradation of Sp1.
    Biochem J. 2000 Jun 1;348 Pt 2:281-9 PMID: 10816420
  3. Regulation of G(1) cyclin-dependent kinases in the mammalian cell cycle.
    Curr Opin Cell Biol. 2000 Dec;12(6):676-84 PMID: 11063931
  4. Role of p27(Kip1) in human intestinal cell differentiation.
    Gastroenterology. 2001 Feb;120(2):423-38 PMID: 11159883
  5. Inhibition of cyclin E-cyclin-dependent kinase 2 complex formation and activity is associated with cell cycle arrest and withdrawal in oligodendrocyte progenitor cells.
    J Neurosci. 2001 Feb 15;21(4):1274-82 PMID: 11160398
  6. Overexpression of p27Kip1 lengthens the G1 phase in a mouse model that targets inducible gene expression to central nervous system progenitor cells.
    Proc Natl Acad Sci U S A. 2001 May 22;98(11):6435-40 PMID: 11371649
  7. Cyclin A-CDK phosphorylates Sp1 and enhances Sp1-mediated transcription.
    EMBO J. 2001 Oct 15;20(20):5737-47 PMID: 11598016
  8. p27(Kip1) enhances myelin basic protein gene promoter activity.
    J Neurosci Res. 2002 Jan 1;67(1):100-5 PMID: 11754085
  9. Regulation of brain-specific transcription of the mouse myelin basic protein gene: function of the NFI-binding site in the distal promoter.
    Biochem Biophys Res Commun. 1990 Mar 16;167(2):648-53 PMID: 1690988
  10. GC box binding induces phosphorylation of Sp1 by a DNA-dependent protein kinase.
    Cell. 1990 Oct 5;63(1):155-65 PMID: 2170018
  11. A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells.
    Nucleic Acids Res. 1991 May 11;19(9):2499 PMID: 2041787
  12. CG-4, a new bipotential glial cell line from rat brain, is capable of differentiating in vitro into either mature oligodendrocytes or type-2 astrocytes.
    J Neurosci Res. 1992 Jan;31(1):193-204 PMID: 1613821
  13. Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle.
    Bioessays. 1995 Jun;17(6):471-80 PMID: 7575488
  14. Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex.
    Nature. 1996 Jul 25;382(6589):325-31 PMID: 8684460
  15. High Sp1/Sp3 ratios in epithelial cells during epithelial differentiation and cellular transformation correlate with the activation of the HPV-16 promoter.
    Virology. 1996 Oct 1;224(1):281-91 PMID: 8862423
  16. 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
  17. 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
  18. The role of p27kip1 in the in vitro differentiation of murine keratinocytes.
    Cell Growth Differ. 1997 Feb;8(2):203-11 PMID: 9040942
  19. Reduced O glycosylation of Sp1 is associated with increased proteasome susceptibility.
    Mol Cell Biol. 1997 May;17(5):2550-8 PMID: 9111324
  20. A unique cathepsin-like protease isolated from CV-1 cells is involved in rapid degradation of retinoblastoma susceptibility gene product, RB, and transcription factor SP1.
    Biochim Biophys Acta. 1997 Apr 10;1351(3):274-86 PMID: 9130591
  21. Casein kinase II-mediated phosphorylation of the C terminus of Sp1 decreases its DNA binding activity.
    J Biol Chem. 1997 May 23;272(21):13489-95 PMID: 9153193
  22. Epidermal growth factor and okadaic acid stimulate Sp1 proteolysis.
    J Biol Chem. 1997 Jun 27;272(26):16540-7 PMID: 9195964
  23. Modulation of transcription factor Sp1 by cAMP-dependent protein kinase.
    J Biol Chem. 1997 Aug 22;272(34):21137-41 PMID: 9261118
  24. Promoting apoptosis: a novel activity associated with the cyclin-dependent kinase inhibitor p27.
    Cancer Res. 1997 Dec 15;57(24):5441-5 PMID: 9407946
  25. Opposite transcriptional effects of cyclic AMP-responsive elements in confluent or p27KIP-overexpressing cells versus serum-starved or growing cells.
    Mol Cell Biol. 1998 Jan;18(1):409-19 PMID: 9418888
  26. Transplantation of CG4 oligodendrocyte progenitor cells in the myelin-deficient rat brain results in myelination of axons and enhanced oligodendroglial markers.
    J Neurosci Res. 1997 Dec 1;50(5):872-87 PMID: 9418974
  27. Ectopic expression of p27Kip1 in oligodendrocyte progenitor cells results in cell-cycle growth arrest.
    J Neurobiol. 1998 Sep 5;36(3):431-40 PMID: 9733077
  28. Growth/cell cycle regulation of Sp1 phosphorylation.
    J Biol Chem. 1999 Jan 15;274(3):1207-15 PMID: 9880488
  29. Neurotransmitter receptor activation triggers p27(Kip1 )and p21(CIP1) accumulation and G1 cell cycle arrest in oligodendrocyte progenitors.
    Development. 1999 Feb;126(5):1077-90 PMID: 9927607
  30. Cip/Kip cyclin-dependent kinase inhibitors: brakes of the cell cycle engine during development.
    Bioessays. 1998 Dec;20(12):1020-9 PMID: 10048302
  31. CDK inhibitors: positive and negative regulators of G1-phase progression.
    Genes Dev. 1999 Jun 15;13(12):1501-12 PMID: 10385618
  32. Sp1 and its likes: biochemical and functional predictions for a growing family of zinc finger transcription factors.
    Ann N Y Acad Sci. 1999 Jun 30;880:94-102 PMID: 10415854
  33. Regulation of myelin basic protein gene transcription by Sp1 and Puralpha: evidence for association of Sp1 and Puralpha in brain.
    J Cell Physiol. 1999 Oct;181(1):160-8 PMID: 10457364
  34. The Sp-family of transcription factors.
    Gene. 1999 Oct 1;238(2):291-300 PMID: 10570957
  35. Cell cycle arrest induced by ectopic expression of p27 is not sufficient to promote oligodendrocyte differentiation.
    J Cell Biochem. 1999 Dec;76(2):270-9 PMID: 10618643
  36. p27kip1 functions as an anergy factor inhibiting interleukin 2 transcription and clonal expansion of alloreactive human and mouse helper T lymphocytes.
    Nat Med. 2000 Mar;6(3):290-7 PMID: 10700231
  37. Reversible G(1) arrest induced by inhibition of the epidermal growth factor receptor tyrosine kinase requires up-regulation of p27(KIP1) independent of MAPK activity.
    J Biol Chem. 2000 Mar 10;275(10):6987-95 PMID: 10702262
  38. Cell-cycle inhibitors: three families united by a common cause.
    Gene. 2000 Apr 18;247(1-2):1-15 PMID: 10773440
  39. The N-terminal domains of cyclin-dependent kinase inhibitory proteins block the phosphorylation of cdk2/Cyclin E by the CDK-activating kinase.
    Biochem Biophys Res Commun. 2000 May 10;271(2):469-73 PMID: 10799321
  40. p27(Kip1) is an inducer of intestinal epithelial cell differentiation.
    Am J Physiol Cell Physiol. 2000 Oct;279(4):C1045-57 PMID: 11003585
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.23.12.4035-4045.2003
Published
2003-06-00
Pages
4035-45
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC156141
Subset
IM
Grants
NCI NIH HHS · R01 CA084325 · United States
NCI NIH HHS · CA84325 · United States
External Links
PubMed source DOI: 10.1128/MCB.23.12.4035-4045.2003 PMC Full Text View journal details
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