The MST1 and hMOB1 tumor suppressors control human centrosome duplication by regulating NDR kinase phosphorylation

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Updated: Jun 19, 2026

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis
08:33

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis

Published on: December 5, 2017

Alexander Hergovich1, Reto S Kohler, Debora Schmitz

  • 1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland. hergo@fmi.ch

Current Biology : CB
|October 20, 2009
PubMed
Abstract

Insights

Human MST1/hMOB1 signaling regulates centrosome duplication by controlling centriole formation. This pathway is essential for normal cell division and involves MST1 kinase activity and NDR/hMOB1 complex function.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Mammalian MST/hSAV/LATS/hMOB tumor suppressor cascades regulate cell death and proliferation.
  • The function of MST/hMOB signaling beyond these roles is largely unknown.
  • Yeast Mob1p's role in spindle pole body duplication suggests a potential role for human MOB proteins in centrosome duplication.

Purpose of the Study:

  • Investigate the role of human MOB proteins in centrosome duplication.
  • Examine the regulation of human centrosome duplication by mammalian MST kinases.
  • Elucidate the signaling pathway involving MOB proteins and MST kinases in centrosome duplication.

Main Methods:

  • Studied six human MOB proteins and five MST kinases.
  • Utilized overexpression and RNAi depletion techniques.
  • Employed shRNA-resistant mutants to analyze protein function and interactions.
  • Investigated the PLK4/HsSAS-6/CP110 centriole assembly machinery.

Main Results:

  • MST1/hMOB1 signaling was found to control centrosome duplication.
  • hMOB1 overexpression led to centrosome overduplication; depletion impaired centriole duplication.
  • An hMOB1/MST1/NDR1 signaling pathway regulating centrosome duplication was delineated.
  • MST1 kinase activity, but not its binding to hSAV/RASSF1A, is crucial for duplication.
  • Normal daughter centriole formation depends on MST1/hMOB1/NDR signaling.

Conclusions:

  • A novel pathway controlling human centriole duplication is proposed.
  • This pathway operates downstream of HsSAS-6 recruitment to centrioles.
  • The findings provide new insights into the regulation of cell division.

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