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Evidence for a role of the JNK cascade in Smad7-mediated apoptosis

A Mazars1, F Lallemand, C Prunier

  • 1INSERM U482, Hôpital Saint-Antoine, 184 Rue du Faubourg Saint-Antoine, 75571 Paris, Cedex 12, France.

The Journal of Biological Chemistry
|July 31, 2001
PubMed

Insights

Smad7 protein activates the c-Jun N-terminal kinase (JNK) cascade, which is crucial for its cell death-inducing function. However, Smad7

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Apoptosis research

Background:

  • Smad proteins mediate transforming growth factor beta (TGF-beta) superfamily signaling.
  • Smad7 inhibits TGF-beta signaling by interacting with the type I TGF-beta receptor.
  • Smad7 has been implicated in sensitizing cells to various forms of cell death.

Purpose of the Study:

  • To investigate the effect of Smad7 on the c-Jun N-terminal kinase (JNK) cascade.
  • To determine the role of the JNK cascade in Smad7's inhibitory and apoptotic functions.

Main Methods:

  • Transient and stable expression of Smad7.
  • Expression of a dominant-interfering mutant of mitogen-activated protein kinase kinase 4 (MKK4).
  • Assessing JNK activation and TGF-beta signaling inhibition.

Main Results:

  • Smad7 expression led to strong and sustained JNK activation.
  • Inhibition of JNK activation did not affect Smad7's inhibition of TGF-beta signaling.
  • Blocking JNK activation impaired Smad7's ability to induce cell death.

Conclusions:

  • Smad7 activates the JNK cascade.
  • Smad7's inhibitory function is independent of the JNK cascade.
  • The JNK cascade is essential for Smad7-mediated potentiation of cell death.

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