Pituitary tumor transforming gene interacts with Sp1 to modulate G1/S cell phase transition.
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 approximately 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.
Tong
Y
Y
Department of Medicine, Cedars-Sinai Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Tan
Y
Y
Zhou
C
C
Melmed
S
S
D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation / Q000379:methods; D024202:Electrophoretic Mobility Shift Assay; D016193:G1 Phase / Q000235:genetics* / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D016196:S Phase / Q000235:genetics* / Q000502:physiology; D064249:Securin; D016329:Sp1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D064249:Securin; D016329:Sp1 Transcription Factor; C578002:pituitary tumor-transforming protein 1, human