Abstract
We have recently shown that Skp2 levels are high in undifferentiated human embryonic stem cells, but decline rapidly following induction of differentiation, thereby leading to accumulation of p27. Changes in Skp2 levels were found to be caused mainly by its rate of degradation. Here we show that the activity of ApC/CCdh1, the ubiquitin ligase that targets Skp2 for degradation, increases markedly during the differentiation process of human embryonic stem cells. ApC/CCdh1 is present but inactive in undifferentiated embryonic stem cells and becomes active in the differentiated state. the rise in ApC/CCdh1 activity with differentiation appears to be due, at least in part, to a dramatic decline in the levels of its inhibitor emi1. In addition, protein kinase activity also appears to contribute to the suppression of ApC/CCdh1 activity in undifferentiated stem cells, possibly by inhibitory phosphorylation of Cdh1.
| Original language | English |
|---|---|
| Pages (from-to) | 1986-1989 |
| Number of pages | 4 |
| Journal | Cell Cycle |
| Volume | 9 |
| Issue number | 10 |
| DOIs | |
| State | Published - 15 May 2010 |
| Externally published | Yes |
Bibliographical note
Funding Information:This study was supported by grants from the Israel Cancer Research Fund through the donation from Michael Walzer and the Israel Chief Scientist Office, Ministry of Health.
Funding
This study was supported by grants from the Israel Cancer Research Fund through the donation from Michael Walzer and the Israel Chief Scientist Office, Ministry of Health.
| Funders | Funder number |
|---|---|
| Israel Cancer Research Fund | |
| Chief Scientist Office | |
| Ministeriet Sundhed Forebyggelse |
Keywords
- APC/C
- Differentiation
- Emi1
- Skp2
- Ubiquitin
- p27