Notch1 modulates timing of G1-S progression by inducing SKP2 transcription and p27 Kip1 degradation.
Notch1 modulates timing of G1-S progression by inducing SKP2 transcription and p27 Kip1 degradation.
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DOI：
10.1084/jem.20050559
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发表时间：
2005-07-04
期刊：
影响因子：
--
通讯作者：
Carlesso N
中科院分区：
文献类型：
--
作者：
Sarmento LM;Huang H;Limon A;Gordon W;Fernandes J;Tavares MJ;Miele L;Cardoso AA;Classon M;Carlesso N
Cyclin-dependent kinase inhibitors (CKIs) and Notch receptor activation have been shown to influence adult stem cells and progenitors by altering stem cell self-renewal and proliferation. Yet, no interaction between these molecular pathways has been defined. Here we show that ligand-independent and ligand-dependent activation of Notch1 induces transcription of the S phase kinase–associated protein 2 (SKP2), the F-box subunit of the ubiquitin-ligase complex SCFSKP2 that targets proteins for degradation. Up-regulation of SKP2 by Notch signaling enhances proteasome-mediated degradation of the CKIs, p27Kip1 and p21Cip1, and causes premature entry into S phase. Silencing of SKP2 by RNA interference in G1 stabilizes p27Kip1 and p21Cip1 and abolishes Notch effect on G1-S progression. Thus, SKP2 serves to link Notch1 activation with the cell cycle machinery. This novel pathway involving Notch/SKP2/CKIs connects a cell surface receptor with proximate mediators of cell cycle activity, and suggests a mechanism by which a known physiologic mediator of cell fate determination interfaces with cell cycle control.
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影响因子：
20.3
作者：
Carlesso, N;Aster, JC;Scadden, DT
通讯作者：
Scadden, DT
影响因子：
20.3
作者：
Mancini, SJC;Mantei, N;Radtke, F
通讯作者：
Radtke, F
影响因子：
21.3
作者：
Carrano, AC;Eytan, E;Pagano, M
通讯作者：
Pagano, M
影响因子：
64.8
作者：
JARRIAULT, S;BROU, C;ISRAEL, A
通讯作者：
ISRAEL, A
DOI：
10.1006/meth.1996.0407
发表时间：
1997-02-01
期刊：
METHODS-A COMPANION TO METHODS IN ENZYMOLOGY
影响因子：
--
作者：
Orlando, V;Strutt, H;Paro, R
通讯作者：
Paro, R