Sp4 Regulates PTTG1IP Gene Transcription and Expression.

Abstract

Pituitary tumor-transforming gene 1 protein (PTTG)-interacting protein, also known as PTTG-binding factor (PBF), is encoded by a proto-oncogene PTTG1IP. PBF has been identified through its interaction with PTTG. Similar to PTTG, PBF has been implicated in the etiology of several tumors, including pituitary, thyroid, and breast cancer. PBF can induce the translocation of PTTG into the nucleus, and then lead to tumorigenesis. Studies have shown that PBF plays a vital and complex role in increasing tumor development. However, the transcriptional regulation of PTTG1IP gene remains undefined. In this study, we have cloned a 467-bp fragment of the 5' flanking region of the human PTTG1IP gene and identified the region (-212 to +7 bp) necessary for PTTG1IP gene promoter activity by luciferase assay. Electrophoretic mobility shift assay revealed PTTG1IP gene promoter containing Sp4 response elements. Overexpression of Sp4 increased PTTG1IP gene transcription and expression in HeLa cells. Our study demonstrates that Sp4 regulates PTTG1IP gene transcription and expression.