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Cell cycle-dependent nuclear export of Cdh1p may contribute to the inactivation of APC/C(Cdh1)

Malika Jaquenoud1, Frank van Drogen, Matthias Peter

  • 1Swiss Institute for Experimental Cancer Research (ISREC), Chemin des Boveresses 155, 1066 Epalinges/VD, Switzerland.

The EMBO Journal
|November 29, 2002
PubMed

Insights

The anaphase-promoting complex (APC/C) subunit Cdh1p

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cdh1p is a key regulator of the cell cycle, acting as a subunit of the anaphase-promoting complex (APC/C).
  • APC/C functions as an E3 ubiquitin ligase, degrading mitotic cyclins like Clb2p during the G1 phase.
  • Cdh1p inactivation at the G1/S transition is primarily mediated by phosphorylation by Cdc28p-Clb5p.

Purpose of the Study:

  • To investigate the subcellular localization dynamics of Cdh1p during the cell cycle.
  • To elucidate the regulatory mechanisms governing Cdh1p nuclear export.
  • To understand the functional significance of Cdh1p localization for APC/C activity.

Main Methods:

  • Cell cycle synchronization and analysis.
  • Immunofluorescence microscopy to track Cdh1p localization.
  • Analysis of Cdh1p interactions with importin Pse1p and exportin Msn5p.
  • Genetic manipulation of msn5 and Cdh1p mutants.

Main Results:

  • Cdh1p localizes to the nucleus during G1 phase and translocates to the cytoplasm from S phase to mitosis.
  • Nuclear export of Cdh1p is phosphorylation-dependent and requires active Cdc28p kinase.
  • Cdh1p interacts with Pse1p and Msn5p, with Msn5p being essential for efficient Cdh1p export.
  • Cells lacking Msn5p exhibit sensitivity to Cdh1p overexpression, and constitutively nuclear Cdh1p mutants cause cell cycle arrest.

Conclusions:

  • Phosphorylation-dependent nuclear export of Cdh1p, mediated by Msn5p, is crucial for efficient APC/C(Cdh1) inactivation.
  • Regulated Cdh1p localization ensures proper cell cycle progression by controlling substrate degradation.
  • These findings highlight a novel regulatory mechanism for APC/C activity through dynamic protein trafficking.

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