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F-box protein Skp2: a novel transcriptional target of E2F

Oncogene volume 25, pages 2615–2627 (2006)Cite this article

Abstract

The F-box-containing protein Skp2 plays a critical role in coordinating the G1/S transition and progression through the S phase of the mammalian cell cycle. Skp2 is overexpressed in a broad spectrum of human cancers and the expression level correlates with tumor malignancy. However, the Skp2 gene is neither amplified nor rearranged in most human cancers and the underlying mechanism of Skp2 overexpression remains poorly understood. We show here that the Skp2 gene contains a functional E2F response element (hSRE2). Ectopic expression of E2F1 induces expression of the endogenous Skp2 gene in human fibroblast cells, whereas antisense-mediated knockdown of E2F1 in human tumor cell lines reduces expression of endogenous Skp2 gene. The hSRE2 element not only participates in activation of Skp2 promoter function during normal cell cycle progression into S phase, it is also required for the high-level Skp2 gene expression in many human tumor cell lines. These results reveal Skp2 as a novel target for E2F regulation that is disrupted in several human tumor cell lines.

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Acknowledgements

We thank Drs Reed Graves, Peter Tontonoz, and Charles Stiles for their critical review of this manuscript. We also like to thank Ms Galina Grechkina for her technical support in EMSA analysis. The work is supported by grant from NIH (CA074907).

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  1. Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, Chicago, IL, USA

    L Zhang & C Wang

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Correspondence to C Wang.

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Zhang, L., Wang, C. F-box protein Skp2: a novel transcriptional target of E2F. Oncogene 25, 2615–2627 (2006). https://doi.org/10.1038/sj.onc.1209286

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