Regulation of the cell cycle inhibitor p27 and its ubiquitin ligase Skp2 in differentiation of human embryonic stem cells

Egozi  D; Shapira  M; Paor  GBen-Izhak  OSkorecki  KHershko  DD

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Regulation of the cell cycle inhibitor p27 and its ubiquitin ligase Skp2 in differentiation of human embryonic stem cells

机译：Regulation of the cell cycle inhibitor p27 and its ubiquitin ligase Skp2 in differentiation of human embryonic stem cells

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Embryonic stem cells combine the features of robust proliferation with precise differentiation capacity. p27 is a cell cycle inhibitor that is involved in the regulation of proliferation and differentiation in many developing tissues. Recent studies in murine embryonic stem cells have suggested that p27 is involved in the progression of normal differentiation programs in these cells. However, the expression and regulation of p27 and its role in the differentiation of human embryonic stem cells ( hESc) has not been previously explored. Herein we show that p27 expression was low in undifferentiated hESc, but increased markedly in differentiated cells. The expression of Skp2, the ubiquitin ligase that targets p27 for degradation, was inversely related to p27 expression. Moreover, embryoid bodies ( EBs) with low p27 expression and high Skp2/ p27 ratio showed poorer differentiation than those with high p27 expression. Modulation of Skp2 expression is mainly regulated by its rate of degradation. In contrast to somatic cells, which have high levels of Skp2 mainly in S and G2/ M, in undifferentiated hESc Skp2 levels were also high in G1. These results point to a potentially important role for p27 regulation in hESc.

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《The FASEB Journal》 |2007年第11期|2807-2817|共11页
作者
Egozi D; Shapira M; Paor GBen-Izhak OSkorecki KHershko DD;
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作者单位

Technion Israel Inst Technol, Rambam Med Ctr, Dept Surg, IL-31096 Haifa, Israel;

Technion Israel Inst Technol, Dept Plast Surg, IL-31096 Haifa, Israel;

Technion Israel Inst Technol, Dept Nephrol, IL-31096 Haifa, IsraelTechnion Israel Inst Technol, Rambam Med Ctr, Dept Pathol, IL-31096 Haifa, IsraelTechnion Israel Inst Technol, Bruce Rappaport Fac Med, IL-31096 Haifa, IsraelTechnion Israel Inst Technol, Res Inst, IL-31096 Haifa, Israel;

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正文语种英语
中图分类生物化学;
关键词
tumorigenesis; cyclin-dependent kinase; hESc differentiation; F-box protein; ubiquitin system; DEPENDENT KINASE INHIBITORS; HUMAN PROSTATE-CANCER; HUMAN BREAST-CANCER; P27(KIP1) DEGRADATION; COLORECTAL CARCINOMAS; SUBUNIT SKP2; PROTEIN; EXPRESSION; GROWTH; TRANSCRIPTION;

Regulation of the cell cycle inhibitor p27 and its ubiquitin ligase Skp2 in differentiation of human embryonic stem cells

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