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Published on: August 25, 2017
Skp2 inversely correlates with p27 and tuberin in transformed cells
M Rosner1, M Hanneder, N Siegel
1Medical Genetics, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Abstract:
The cyclin-dependent kinase inhibitor p27Kip1 (p27) is a major gatekeeper of the mammalian cell cycle progression known to be regulated by both, its subcellular localization and its degradation. To allow entrance into S phase and thereby mammalian cell cycle progression p27 must be degraded by a skp2-containing E3 ubiquitin ligase whose task is to target p27 for degradation by the proteasome. The tumor suppressor gene product tuberin directly binds to p27 and protects it from degradation via skp2. Whereas, p27 and tuberin are known to be localized to both, the cytoplasm and the nucleus, the localization of skp2 remained elusive. Here we demonstrate that skp2 is a cytoplasmic and nuclear protein. In addition we found an inverse correlation of the endogenous protein levels of skp2 with p27 and tuberin in different transformed cells and under different growth conditions. These data allow new important insights into this molecular network of cell cycle control.
Insights
The skp2 protein, crucial for cell cycle progression, is found in both the cytoplasm and nucleus. Its levels inversely correlate with p27Kip1 (p27) and tuberin, offering new insights into cell cycle control.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- p27Kip1 (p27) regulates mammalian cell cycle progression by controlling entry into S phase.
- p27 degradation by skp2-containing E3 ubiquitin ligase targets it for proteasomal degradation.
- Tuberin binds p27, protecting it from skp2-mediated degradation.
Purpose of the Study:
- To investigate the subcellular localization of skp2.
- To explore the relationship between skp2, p27, and tuberin levels in cell cycle control.
Main Methods:
- Immunoblotting to detect endogenous protein levels.
- Cellular fractionation to determine subcellular localization.
Main Results:
- skp2 is localized in both the cytoplasm and nucleus.
- An inverse correlation was observed between endogenous skp2 levels and p27/tuberin levels in transformed cells.
- This inverse correlation was also noted under various growth conditions.
Conclusions:
- skp2's dual localization provides a more complete understanding of its role in cell cycle regulation.
- The inverse correlation suggests a dynamic interplay between skp2, p27, and tuberin in controlling cell cycle progression.
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