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Pituitary tumor transforming gene interacts with Sp1 to modulate G1/S cell phase transition

Oncogene volume 26, pages 5596–5605 (2007)Cite this article

Abstract

Pituitary tumor transforming gene (PTTG1) was isolated from rat pituitary tumor cells, and subsequently identified as a securin protein as well as a transcription factor. We show here a global transcriptional effect of PTTG1 in human choriocarcinoma JEG-3 cells by simultaneously assessing 20 000 gene promoters using chromatin immunoprecipitation (ChIP)-on-Chip experiments. Seven hundred and forty-six gene promoters (P<0.001) were found enriched, with functions relating to cell cycle, metabolic control and signal transduction. Significant interaction between PTTG1 and Sp1 (P<0.000001) was found by transcriptional pattern analysis of ChIP data and further confirmed by immunoprecipitation and pull-down assays. PTTG1 acts coordinately with Sp1 to induce cyclin D3 expression ∼threefold, and promotes G1/S-phase transition independently of p21. PTTG1 deletion was also protective for anchorage-independent cell colony formation. The results show that PTTG1 exhibits properties of a global transcription factor, and specifically modulates the G1/S-phase transition by interacting with Sp1. This novel signaling pathway may be required for PTTG1 transforming activity.

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Abbreviations

ChIP:

chromatin immunoprecipitation

MEF:

mouse embryo fibroblast

PTTG:

pituitary tumor transforming gene

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Acknowledgements

p21−/− HCT116 cells were kindly provided by Dr Bert Vogelstein, Johns Hopkins University. Mouse embryos were kindly provided by Vera Chesnokova. Retroviral plasmids pBabe-ras, pWZL-E1A, pWZL-Myc and pWZL-T-Ag were from Dr Pandolfi, Memorial Sloan-Kettering Cancer Center. This work was supported by NIH Grant CA 75979 (SM) and The Doris Factor Molecular Endocrinology Laboratory.

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  1. Department of Medicine, Cedars-Sinai Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Y Tong, Y Tan, C Zhou & S Melmed

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  1. Y Tong
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Correspondence to S Melmed.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Tong, Y., Tan, Y., Zhou, C. et al. Pituitary tumor transforming gene interacts with Sp1 to modulate G1/S cell phase transition. Oncogene 26, 5596–5605 (2007). https://doi.org/10.1038/sj.onc.1210339

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