Startseite Transcription factor FOXM1c is repressed by RB and activated by cyclin D1/Cdk4
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Transcription factor FOXM1c is repressed by RB and activated by cyclin D1/Cdk4

  • Inken Wierstra und Jürgen Alves
Veröffentlicht/Copyright: 20. Juli 2006
Biological Chemistry
Aus der Zeitschrift Band 387 Heft 7

Abstract

The proliferation-stimulating transactivator FOXM1c (MPP2) is repressed by RB and activated by cyclin D1/Cdk4 and therefore behaves like E2F. Despite its strong transactivation domain, FOXM1c is kept almost inactive by two different inhibitory domains, the N-terminus and the central domain. The tumor suppressor RB binds directly to the central domain of FOXM1c and thereby indirectly represses the transactivation domain, so that the central domain of FOXM1c functions as an RB-recruiting negative-regulatory domain. Cyclin D1/Cdk4 releases FOXM1c from this repression by RB and from the repression by its own inhibitory N-terminus, thereby strongly activating FOXM1c. However, cyclin D1/Cdk4 does not directly affect the transactivation domain or the DNA-binding domain. By phosphorylation of RB, but not FOXM1c, cyclin D1/Cdk4 interrupts their direct interaction and thus abrogates the repression of FOXM1c by RB. Cyclin D1/Cdk4 also eliminates the inhibition of the transactivation domain by the N-terminus of FOXM1c, probably by interruption of their direct interaction. Consequently, the G1-phase proliferation signal cyclin D1/Cdk4 converts FOXM1c from an almost inactive form into a strong transactivator in G1-phase, i.e., just at the time point at which the transcriptional activity of FOXM1 is required for stimulation of the G1/S-transition.

Keywords: cyclin D1/Cdk4; cyclin E/Cdk2; FOXM1c; RB
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Corresponding author

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Published Online: 2006-07-20
Published in Print: 2006-07-01

©2006 by Walter de Gruyter Berlin New York

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https://doi.org/10.1515/BC.2006.119
Schlagwörter für diesen Artikel
cyclin D1/Cdk4; cyclin E/Cdk2; FOXM1c; RB

Artikel in diesem Heft

  1. 4th General Meeting of the International Proteolysis Society/International Conference on Protease Inhibitors
  2. Extracellular granzymes: current perspectives
  3. Impact of the N-terminal amino acid on targeted protein degradation
  4. Structural aspects of recently discovered viral deubiquitinating activities
  5. Cysteine cathepsins and caspases in silicosis
  6. The proprotein convertases and their implication in sterol and/or lipid metabolism
  7. PREPL: a putative novel oligopeptidase propelled into the limelight
  8. Human cathepsin L rescues the neurodegeneration and lethality in cathepsin B/L double-deficient mice
  9. Helicobacter pylori-induced downregulation of the secretory leukocyte protease inhibitor (SLPI) in gastric epithelial cell lines and its functional relevance for H. pylori-mediated diseases
  10. Increased local levels of granulocyte colony-stimulating factor are associated with the beneficial effect of pre-elafin (SKALP/trappin-2/WAP3) in experimental emphysema
  11. Interaction of a novel form of Pseudomonas aeruginosa alkaline protease (aeruginolysin) with interleukin-6 and interleukin-8
  12. Analysis of aldosterone-induced differential receptor-independent protein patterns using 2D-electrophoresis and mass spectrometry
  13. Modeling the 3D structure of wheat subtilisin/chymotrypsin inhibitor (WSCI). Probing the reactive site with two susceptible proteinases by time-course analysis and molecular dynamics simulations
  14. A stable analogue of glucose-dependent insulinotropic polypeptide, GIP(LysPAL16), enhances functional differentiation of mouse embryonic stem cells into cells expressing islet-specific genes and hormones
  15. Transcription factor FOXM1c is repressed by RB and activated by cyclin D1/Cdk4
  16. Despite its strong transactivation domain, transcription factor FOXM1c is kept almost inactive by two different inhibitory domains
  17. Inhibition of calcineurin by infusion of CsA causes hyperphosphorylation of tau and is accompanied by abnormal behavior in mice
  18. Isolation and properties of extracellular proteinases of Penicillium marneffei
  19. Isolation and comparative characterization of Ki-67 equivalent antibodies from the HuCAL® phage display library
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