Mammalian Cdh1/Fzr mediates its own degradation

Tamar Listovsky, Yifat S. Oren, Yana Yudkovsky, Hiro M. Mahbubani, Aryeh M. Weiss, Mario Lebendiker, Michael Brandeis

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

The Anaphase-Promoting Complex/Cyclosome (APC/C) ubiquitin ligase mediates degradation of cell cycle proteins during mitosis and G1. Cdc20/Fzy and Cdh1/ Fzr are substrate-specific APC/C activators. The level of mammalian Cdh1 is high in mitosis, but it is inactive and does not bind the APC/C. We show that when Cdh1 is active in G1 and G0, its levels are considerably lower and almost all of it is APC/C associated. We demonstrate that Cdh1 is subject to APC/C-specific degradation in G1 and G0, and that this degradation depends upon two RXXL-type destruction boxes. We further demonstrate that addition of Cdh1 to Xenopus interphase extracts, which have an inactive APC/C, activates it to degrade Cdh1. These observations indicate that Cdh1 mediates its own degradation by activating the APC/C to degrade itself. Elevated levels of Cdh1 are deleterious for cell cycle progression in various organisms. This auto-regulation of Cdh1 could thus play a role in ensuring that the level of Cdh1 is reduced during G1 and GO, allowing it to be switched off at the correct time.

Original languageEnglish
Pages (from-to)1619-1626
Number of pages8
JournalEMBO Journal
Volume23
Issue number7
DOIs
StatePublished - 7 Apr 2004
Externally publishedYes

Keywords

  • APC/C
  • Cyclosome
  • Destruction box
  • Fizzy
  • Fizzy-related

Fingerprint

Dive into the research topics of 'Mammalian Cdh1/Fzr mediates its own degradation'. Together they form a unique fingerprint.

Cite this