Discovery of a distinct domain in cyclin A sufficient for centrosomal localization independently of Cdk binding

Gaetan Pascreau, Frank Eckerdt, Mair E A Churchill, James L. Maller

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Centrosomes have recently emerged as key regulators of the cell cycle. The G1/S transition requires a functional centrosome, and centrosomal localization of numerous proteins, including cyclin/Cdk complexes, is important for the G2/M transition. Here we identify a modular centrosomal localization signal (CLS) localizing cyclin A to centrosomes independently of Cdk binding. The cyclin A CLS is located in a distinct part of the molecule compared with the cyclin E CLS and includes the MRAIL hydrophobic patch involved in substrate recognition. The cyclin A CLS interacts with p27KIP1, and expression of p 27KIP1 removes cyclin A but not cyclin E from centrosomes. Expression of the cyclin A CLS displaces both endogenous cyclin A and E from centrosomes and inhibits DNA replication, supporting an emerging concept that DNA replication is linked to centrosomal events. Structural analysis indicates that differences in surface charge and length of the C-terminal helix explain why the MRAIL region in cyclin E is not a functional CLS. These results indicate that the cyclin A CLS may contribute to targeting and recognition of centrosomal Cdk substrates and is required for specific effects of p27KIP1 on cyclin A-Cdk2.

Original languageEnglish (US)
Pages (from-to)2932-2937
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number7
DOIs
StatePublished - Feb 16 2010

Keywords

  • Cell cycle
  • Centrosomal localization signal
  • Hydrophobic patch
  • p27

ASJC Scopus subject areas

  • General

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