Nuclear import of cubitus interruptus is regulated by hedgehog via a mechanism distinct from Ci stabilization and Ci

Q T Wang1, R A Holmgren

  • 1Department of Biochemistry, Molecular Biology and Cell Biology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Evanston, Illinois 60208, USA.

Development (Cambridge, England)
|June 23, 2000
PubMed

Insights

Hedgehog (Hh) signaling regulates Cubitus interruptus (Ci) protein transport into the nucleus, distinct from its stabilization and activation. This study clarifies how Hh controls Ci

Area of Science:

  • Developmental Biology
  • Cell Signaling
  • Molecular Biology

Background:

  • The Hedgehog (Hh) pathway is crucial for specifying cell fates in Drosophila wings.
  • Cubitus interruptus (Ci) is a key transcription factor in the Hh pathway.
  • Hh signaling regulates the processing and activity of Ci, but the precise mechanisms are complex.

Purpose of the Study:

  • To investigate the in vivo mechanism of Ci nuclear import.
  • To elucidate the relationship between Hh-mediated Ci nuclear import, stabilization, and activation.
  • To identify distinct regulatory steps in the Hh signaling pathway.

Main Methods:

  • In vivo analysis of Ci protein localization and activity in Drosophila.
  • Hedgehog signaling pathway manipulation.
  • Assessment of Ci protein stabilization and nuclear translocation.

Main Results:

  • Hh signaling is required for rapid Ci nuclear import in cells near the anteroposterior boundary.
  • Ci nuclear import is regulated by Hh independently of Ci stabilization.
  • Ci stabilization and rapid nuclear import do not guarantee maximal Ci activity, indicating distinct regulatory mechanisms.
  • Cos2 and PKA play positive roles in Hh-induced Ci activation.

Conclusions:

  • Nuclear import, stabilization, and activation of Ci are regulated by distinct mechanisms.
  • Hh signaling controls Ci nuclear import independently of stabilization.
  • Cos2 and PKA are positive regulators of Ci activation in response to Hh.

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