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Identification of multiple CDH1 homologues in vertebrates conferring different substrate specificities

Y Wan1, M W Kirschner

  • 1Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

Proceedings of the National Academy of Sciences of the United States of America
|November 1, 2001
PubMed

Insights

Multiple CDH1 genes in chicks activate the anaphase-promoting complex (APC), regulating cell division. These novel genes show distinct tissue localization and varying activities, suggesting complex cell cycle control.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • The anaphase-promoting complex (APC) is crucial for cell cycle progression, particularly mitosis and G1 phase.
  • APC activity is regulated by co-activators like CDC20 and CDH1, which target substrates for degradation.
  • Understanding the regulation of APC is key to comprehending cell cycle control and its dysregulation in diseases.

Purpose of the Study:

  • To identify and characterize functional CDH1 homologues in the chick.
  • To investigate the expression patterns and cellular localization of these novel CDH1 genes.
  • To determine the in vitro and cellular activities of chick CDH1 proteins in APC-mediated ubiquitination.

Main Methods:

  • Identification and cloning of chick CDH1 homologues.
  • Analysis of transcript localization in various chick tissues (proliferating, differentiated, postmitotic).
  • In vitro binding assays and co-immunoprecipitation to assess complex formation with APC.
  • In vitro ubiquitination assays to quantify the activity of different CDH1 proteins on APC substrates.

Main Results:

  • Discovery of multiple functional CDH1 homologues in the chick.
  • Differential localization of CDH1 transcripts in specific tissue types.
  • Demonstration that all identified chick CDH1 proteins form complexes with APC.
  • Quantification of distinct ubiquitination activities among the different CDH1 proteins towards APC substrates.

Conclusions:

  • Multiple CDH1 proteins exist in the chick, each potentially contributing to APC regulation.
  • Differential expression and activity of CDH1 homologues suggest precise temporal and spatial control of APC.
  • These findings expand our understanding of cell cycle regulation beyond known mechanisms, involving multiple CDH1 isoforms.

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