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Notch Activation by Shootin1 Opposing Activities on 2 Ubiquitin Ligases

Tamar Sapir1, Talia Levy1, Noga Kozer2

  • 1Department of Molecular Genetics, Weizmann Institute of Science, 234 Herzl St., Rehovot, Israel.

Cerebral Cortex (New York, N.Y. : 1991)
|October 6, 2017
PubMed

Insights

Shootin1 surprisingly activates the Notch pathway by modulating ubiquitin ligases. It influences neuroblast cell fate in the developing brain through opposing actions on these key regulators.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Molecular Biology

Background:

  • The Notch pathway is crucial for stem cell renewal and cell fate determination.
  • Notch signaling is activated by cell-cell contact and regulated by protein degradation.
  • Ubiquitin ligases play a role in controlling Notch pathway activity.

Purpose of the Study:

  • To investigate the role of Shootin1 in Notch pathway regulation.
  • To understand how Shootin1 modulates ubiquitin ligases to control Notch signaling.
  • To elucidate Shootin1's function in neuroblast cell fate determination.

Main Methods:

  • Investigated Shootin1's interaction with LNX1/2 and Itch.
  • Assessed the impact of Shootin1 on Numb and NICD poly-ubiquitination.
  • Examined Shootin1's role in neuroblast cell fate in the developing brain.

Main Results:

  • Shootin1 activates the Notch pathway through dual mechanisms involving ubiquitin ligases.
  • Shootin1 promotes Numb poly-ubiquitination via LNX1/2.
  • Shootin1 inhibits NICD poly-ubiquitination via Itch, leading to opposing effects on Notch signaling.

Conclusions:

  • Shootin1 acts as a novel regulator of the Notch pathway with opposing effects on ubiquitin ligases.
  • Shootin1's dual activity on ubiquitin ligases differentially controls Notch signaling components.
  • Shootin1 plays a significant role in modulating neuroblast cell fate determination in the developing brain.

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