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Identification of c-myc as a down-stream target for pituitary tumor-transforming gene
1Division of Endocrinology and Metabolism, Cedars-Sinai Research Institute, UCLA School of Medicine, Los Angeles, California 90048, USA. pei@cshs.org
Abstract:
Pituitary tumor-transforming gene (PTTG) encodes a protein implicated in cellular transformation and transcriptional regulation. To identify downstream target genes, I established cell lines with tightly regulated inducible expression of PTTG. DNA arrays were used to analyze gene expression profiles after PTTG induction. I identified c-myc oncogene as a major PTTG target. Induction of PTTG resulted in increased cell proliferation through activation of c-myc. I showed that PTTG activates c-myc transcription in transfected cells. PTTG binds to c-myc promoter near the transcription initiation site in a protein complex containing the upstream stimulatory factor (USF1). I have defined the PTTG DNA-binding site and mapped PTTG DNA binding domain to a region between amino acids 61 and 118. Furthermore, I demonstrated that PTTG DNA binding is required for its transcriptional activation function. These results definitively established the role of PTTG as a transcription activator and indicate that PTTG is involved in cellular transformation and tumorigenesis through activation of c-myc oncogene.
Insights
Pituitary tumor-transforming gene (PTTG) activates the c-myc oncogene, driving cell proliferation and contributing to tumorigenesis. This study defines PTTG's role as a transcription activator via c-myc regulation.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Pituitary tumor-transforming gene (PTTG) is linked to cellular transformation and transcriptional regulation.
- Understanding PTTG's downstream targets is crucial for elucidating its role in tumorigenesis.
Purpose of the Study:
- To identify downstream target genes of PTTG.
- To elucidate the mechanism by which PTTG influences cellular transformation and proliferation.
Main Methods:
- Established inducible PTTG expression cell lines.
- Utilized DNA arrays for gene expression profiling.
- Performed transfection assays and DNA-binding studies.
Main Results:
- Identified the c-myc oncogene as a major PTTG target.
- Demonstrated PTTG induction increases cell proliferation via c-myc activation.
- Showed PTTG binds the c-myc promoter and activates its transcription.
Conclusions:
- PTTG functions as a transcription activator, specifically targeting the c-myc oncogene.
- PTTG-mediated activation of c-myc contributes to cellular transformation and tumorigenesis.
- PTTG's DNA-binding domain (amino acids 61-118) is essential for its transcriptional activity.