Securin degradation is mediated by fzy and fzr, and is required for complete chromatid separation but not for cytokinesis

A. Zur, M. Brandeis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

201 Scopus citations

Abstract

We have studied the ubiquitination and degradation patterns of the human securin/PTTG protein. We show that, in contrast to budding yeast pds1, securin degradation is catalyzed by both fzy (fizzy/cdc20) and fzr (fizzy-related/cdh1/hct1). Both fzy and fzr also induce the APC/C to ubiquitinate securin in vitro. Securin degradation is mediated by an RXXL destruction box and a KEN box, and is inhibited only when both sequences are mutated. Interestingly, the non-degradable securin mutant is also partially ubiquitinated by fzy and fzr in vitro. Expressing the non-degradable securin mutant in cells frequently resulted in incomplete chromatid separation and gave rise to daughter cells connected by a thin chromatin fiber, presumably of chromosomes that failed to split completely. Strikingly, the mutant securin did not prevent the majority of sister chromatids from separating completely, nor did it prevent mitotic cyclin degradation and cytokinesis. This phenotype, reminiscent of the fission yeast cut (cells untimely torn) phenotype, is reported here for the first time in mammals.

Original languageAmerican English
Pages (from-to)792-801
Number of pages10
JournalEMBO Journal
Volume20
Issue number4
DOIs
StatePublished - 15 Feb 2001

Keywords

  • APC
  • Cyclosome
  • Fizzy
  • PTTG
  • Securin

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