Abstract
Sp1 binding sites have been identified in enhancer/promoter regions of several growth and cell cycle regulated genes, and it has been shown that Sp1 is increasingly phosphorylated in G1 phase of the cell cycle. Interactions of Sp1 with proteins involved in control of cell cycle and tumor formation have been reported. Here we show that expression of Sp1 protein predominates in the G1 phase of the cell cycle in epithelial cells. This is achieved by proteasome-dependent degradation. Inhibition of endogeneous Sp1 activity by a dominant-negative Sp1 mutant was associated with a cell cycle arrest in G1 phase, a strongly reduced expression of cyclin D1, the EGF-receptor and increased levels of p27Kip1. We have thus identified Sp1 as an important regulator of the cell cycle in G1 phase.
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Acknowledgements
We thank Prof Bernd Dörken for insightful discussions. We also thank Dr G Thiel for the pEBG-Sp1 and pSBII(GC)4CAT DNA constructs. This work was funded by the Deutsche Forschungsgemeinschaft by grants Ro 945/2-3 and Ro 945/2-4 to HD Royer, and by a research grant of the Medical School of the University of Düsseldorf to E Grinstein.
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Grinstein, E., Jundt, F., Weinert, I. et al. Sp1 as G1 cell cycle phase specific transcription factor in epithelial cells. Oncogene 21, 1485–1492 (2002). https://doi.org/10.1038/sj.onc.1205211
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DOI: https://doi.org/10.1038/sj.onc.1205211
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