Multiple anaphase-promoting complex/cyclosome degrons mediate the degradation of human sgo1

Zemfira Karamysheva, Laura A. Diaz-Martinez, Sara E. Crow, Bing Li, Hongtao Yu

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Shugoshin 1 (Sgo1) protects centromeric sister-chromatid cohesion in early mitosis and, thus, prevents premature sister-chromatid separation. The protein level of Sgo1 is regulated during the cell cycle; it peaks in mitosis and is down-regulated in G 1/S. Here we show that Sgo1 is degraded during the exit from mitosis, and its degradation depends on the anaphase-promoting complex/cyclosome (APC/C). Overexpression of Cdh1 reduces the protein levels of ectopically expressed Sgo1 in human cells. Sgo1 is ubiquitinated by APC/C bound to Cdh1 (APC/C Cdh1) in vitro. We have further identified two functional degradation motifs in Sgo1; that is, a KEN (Lys-Glu-Asn) box and a destruction box (D box). Although removal of either motif is not sufficient to stabilize Sgo1, Sgo1 with both KEN box and D box deleted is stable in cells. Surprisingly, mitosis progresses normally in the presence of non-degradable Sgo1, indicating that degradation of Sgo1 is not required for sister-chromatid separation or mitotic exit. Finally, we show that the spindle checkpoint kinase Bub1 contributes to the maintenance of Sgo1 steady-state protein levels in an APC/C- independent mechanism.

Original languageEnglish (US)
Pages (from-to)1772-1780
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number3
DOIs
StatePublished - Jan 16 2009

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Anaphase-Promoting Complex-Cyclosome
Mitosis
Chromatids
Cdh1 Proteins
Degradation
Cells
Proteins
Phosphotransferases
Cell Cycle
Maintenance

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Multiple anaphase-promoting complex/cyclosome degrons mediate the degradation of human sgo1. / Karamysheva, Zemfira; Diaz-Martinez, Laura A.; Crow, Sara E.; Li, Bing; Yu, Hongtao.

In: Journal of Biological Chemistry, Vol. 284, No. 3, 16.01.2009, p. 1772-1780.

Research output: Contribution to journalArticle

Karamysheva, Zemfira ; Diaz-Martinez, Laura A. ; Crow, Sara E. ; Li, Bing ; Yu, Hongtao. / Multiple anaphase-promoting complex/cyclosome degrons mediate the degradation of human sgo1. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 3. pp. 1772-1780.
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