<it>PTTG</it>/securin activates expression of <it>p53 </it>and modulates its function
<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 i...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2004-07-01
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| Series: | Molecular Cancer |
| Online Access: | http://www.molecular-cancer.com/content/3/1/18 |
| _version_ | 1817994192188604416 |
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| author | Hamid Tariq Kakar Sham S |
| author_facet | Hamid Tariq Kakar Sham S |
| author_sort | Hamid Tariq |
| collection | DOAJ |
| description | <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> |
| first_indexed | 2024-04-14T01:49:39Z |
| format | Article |
| id | doaj.art-6de513fe809743c59919fa4e98a78264 |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-04-14T01:49:39Z |
| publishDate | 2004-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-6de513fe809743c59919fa4e98a782642022-12-22T02:19:24ZengBMCMolecular Cancer1476-45982004-07-01311810.1186/1476-4598-3-18<it>PTTG</it>/securin activates expression of <it>p53 </it>and modulates its functionHamid TariqKakar Sham S<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>http://www.molecular-cancer.com/content/3/1/18 |
| spellingShingle | Hamid Tariq Kakar Sham S <it>PTTG</it>/securin activates expression of <it>p53 </it>and modulates its function Molecular Cancer |
| title | <it>PTTG</it>/securin activates expression of <it>p53 </it>and modulates its function |
| title_full | <it>PTTG</it>/securin activates expression of <it>p53 </it>and modulates its function |
| title_fullStr | <it>PTTG</it>/securin activates expression of <it>p53 </it>and modulates its function |
| title_full_unstemmed | <it>PTTG</it>/securin activates expression of <it>p53 </it>and modulates its function |
| title_short | <it>PTTG</it>/securin activates expression of <it>p53 </it>and modulates its function |
| title_sort | it pttg it securin activates expression of it p53 it and modulates its function |
| url | http://www.molecular-cancer.com/content/3/1/18 |
| work_keys_str_mv | AT hamidtariq itpttgitsecurinactivatesexpressionofitp53itandmodulatesitsfunction AT kakarshams itpttgitsecurinactivatesexpressionofitp53itandmodulatesitsfunction |