p27(Kip1) inhibits tissue factor expression

Alexander Breitenstein1, Alexander Akhmedov, Giovanni G Camici

  • 1Cardiology, University Heart Center, University Hospital Zurich, Switzerland; Cardiovascular Research, Physiology Institute, University of Zurich, Switzerland; Center for Integrative Human Physiology (ZHIP), University of Zurich, Switzerland.

Abstract

Insights

The cyclin-dependent kinase inhibitor p27(Kip1) was found to reduce tissue factor (TF) expression in human aortic endothelial cells. This suggests p27(Kip1) may play a role in inhibiting atherosclerosis and vascular remodeling.

Area of Science:

  • Vascular Biology
  • Cell Cycle Regulation
  • Coagulation Cascade

Background:

  • p27(Kip1) is a cyclin-dependent kinase inhibitor that regulates cell proliferation and is implicated in inhibiting atherosclerosis and vascular remodeling.
  • Tissue factor (TF) initiates the coagulation cascade and its expression is associated with atherosclerosis.
  • The relationship between p27(Kip1) and TF expression has not been previously investigated.

Purpose of the Study:

  • To investigate the effect of p27(Kip1) on tissue factor (TF) expression in human aortic endothelial cells.

Main Methods:

  • Overexpression of p27(Kip1) in human aortic endothelial cells using adenoviral transfection.
  • Quiescence of cells followed by stimulation with TNF-α.
  • Assessment of TF protein expression, activity, mRNA levels, and promoter activity.

Main Results:

  • p27(Kip1) overexpression significantly reduced TF protein expression and activity.
  • p27(Kip1) overexpression decreased cytokine-induced TF mRNA expression.
  • TF promoter activity was reduced by p27(Kip1) overexpression, while MAP kinase activation remained unaffected.

Conclusions:

  • p27(Kip1) inhibits TF expression at the transcriptional level.
  • These findings suggest an interaction between p27(Kip1) and TF in pathological processes like atherosclerosis and vascular remodeling.

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...