<it>PTTG</it>/securin activates expression of <it>p53 </it>and modulates its function

• Main Authors: Hamid Tariq, Kakar Sham S
• Format: Article
• Language: English
• Published: BMC 2004-07-01
• Series: Molecular Cancer
• Online Access: http://www.molecular-cancer.com/content/3/1/18

<p>Abstract</p> <p>Background</p> <p>Pituitary tumor transforming gene (<it>PTTG</it>) is a novel oncogene that is expressed abundantly in most tumors. Overexpression of <it>PTTG </it>induces cellular transformation and promotes tumor formation in nude mice. <it>PTTG </it>has been implicated in various cellular processes including sister chromatid separation during cell division as well as induction of apoptosis through <it>p53</it>-dependent and <it>p53</it>-independent mechanisms. The relationship between <it>PTTG </it>and <it>p53 </it>remains unclear, however.</p> <p>Results</p> <p>Here we report the effects of overexpression of <it>PTTG </it>on the expression and function of <it>p53</it>. Our results indicate that overexpression of <it>PTTG </it>regulates the expression of the <it>p53 </it>gene at both the transcriptional and translational levels and that this ability of <it>PTTG </it>to activate the expression of <it>p53 </it>gene is dependent upon the <it>p53 </it>status of the cell. Deletion analysis of the <it>p53 </it>gene promoter revealed that only a small region of the <it>p53 </it>gene promoter is required for its activation by <it>PTTG </it>and further indicated that the activation of <it>p53 </it>gene by <it>PTTG </it>is an indirect effect that is mediated through the regulation of the expression of <it>c-myc</it>, which then interacts with the <it>p53 </it>gene promoter. Our results also indicate that overexpression of <it>PTTG </it>stimulates expression of the Bax gene, one of the known downstream targets of <it>p53</it>, and induces apoptosis in a human embryonic kidney cell line (HEK293). This stimulation of <it>bax </it>expression by <it>PTTG </it>is indirect and is mediated through modulation of <it>p53 </it>gene expression.</p> <p>Conclusions</p> <p>Overexpression of <it>PTTG </it>activates the expression of <it>p53 </it>and modulates its function, with this action of <it>PTTG </it>being mediated through the regulation of <it>c-myc </it>expression. <it>PTTG </it>also up-regulates the activity of the <it>bax </it>promoter and increases the expression of <it>bax </it>through modulation of <it>p53 </it>expression.</p>