Crucial role of TSC-22 in preventing the proteasomal degradation of p53 in cervical cancer.
The p53 tumor suppressor function can be compromised in many tumors by the cellular antagonist HDM2 and human papillomavirus oncogene E6 that induce p53 degradation. Restoration of p53 activity has strong therapeutic potential. Here, we identified TSC-22 as a novel p53-interacting protein and show i...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3411576?pdf=render |
| _version_ | 1818452239734276096 |
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| author | Cheol-Hee Yoon Seung Bae Rho Seong-Tae Kim Seongho Kho Junsoo Park Ik-Soon Jang Seonock Woo Sung Soon Kim Je-Ho Lee Seung-Hoon Lee |
| author_facet | Cheol-Hee Yoon Seung Bae Rho Seong-Tae Kim Seongho Kho Junsoo Park Ik-Soon Jang Seonock Woo Sung Soon Kim Je-Ho Lee Seung-Hoon Lee |
| author_sort | Cheol-Hee Yoon |
| collection | DOAJ |
| description | The p53 tumor suppressor function can be compromised in many tumors by the cellular antagonist HDM2 and human papillomavirus oncogene E6 that induce p53 degradation. Restoration of p53 activity has strong therapeutic potential. Here, we identified TSC-22 as a novel p53-interacting protein and show its novel function as a positive regulator of p53. We found that TSC-22 level was significantly down-regulated in cervical cancer tissues. Moreover, over-expression of TSC-22 was sufficient to inhibit cell proliferation, promote cellular apoptosis in cervical cancer cells and suppress growth of xenograft tumors in mice. Expression of also TSC-22 enhanced the protein level of p53 by protecting it from poly-ubiquitination. When bound to the motif between amino acids 100 and 200 of p53, TSC-22 inhibited the HDM2- and E6-mediated p53 poly-ubiquitination and degradation. Consequently, ectopic over-expression of TSC-22 activated the function of p53, followed by increased expression of p21(Waf1/Cip1) and PUMA in human cervical cancer cell lines. Interestingly, TSC-22 did not affect the interaction between p53 and HDM2. Knock-down of TSC-22 by small interfering RNA clearly enhanced the poly-ubiquitination of p53, leading to the degradation of p53. These results suggest that TSC-22 acts as a tumor suppressor by safeguarding p53 from poly-ubiquitination mediated-degradation. |
| first_indexed | 2024-12-14T21:19:56Z |
| format | Article |
| id | doaj.art-b7b215fcc1bd4d70b7eba8e1b9be59fd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T21:19:56Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b7b215fcc1bd4d70b7eba8e1b9be59fd2022-12-21T22:46:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4200610.1371/journal.pone.0042006Crucial role of TSC-22 in preventing the proteasomal degradation of p53 in cervical cancer.Cheol-Hee YoonSeung Bae RhoSeong-Tae KimSeongho KhoJunsoo ParkIk-Soon JangSeonock WooSung Soon KimJe-Ho LeeSeung-Hoon LeeThe p53 tumor suppressor function can be compromised in many tumors by the cellular antagonist HDM2 and human papillomavirus oncogene E6 that induce p53 degradation. Restoration of p53 activity has strong therapeutic potential. Here, we identified TSC-22 as a novel p53-interacting protein and show its novel function as a positive regulator of p53. We found that TSC-22 level was significantly down-regulated in cervical cancer tissues. Moreover, over-expression of TSC-22 was sufficient to inhibit cell proliferation, promote cellular apoptosis in cervical cancer cells and suppress growth of xenograft tumors in mice. Expression of also TSC-22 enhanced the protein level of p53 by protecting it from poly-ubiquitination. When bound to the motif between amino acids 100 and 200 of p53, TSC-22 inhibited the HDM2- and E6-mediated p53 poly-ubiquitination and degradation. Consequently, ectopic over-expression of TSC-22 activated the function of p53, followed by increased expression of p21(Waf1/Cip1) and PUMA in human cervical cancer cell lines. Interestingly, TSC-22 did not affect the interaction between p53 and HDM2. Knock-down of TSC-22 by small interfering RNA clearly enhanced the poly-ubiquitination of p53, leading to the degradation of p53. These results suggest that TSC-22 acts as a tumor suppressor by safeguarding p53 from poly-ubiquitination mediated-degradation.http://europepmc.org/articles/PMC3411576?pdf=render |
| spellingShingle | Cheol-Hee Yoon Seung Bae Rho Seong-Tae Kim Seongho Kho Junsoo Park Ik-Soon Jang Seonock Woo Sung Soon Kim Je-Ho Lee Seung-Hoon Lee Crucial role of TSC-22 in preventing the proteasomal degradation of p53 in cervical cancer. PLoS ONE |
| title | Crucial role of TSC-22 in preventing the proteasomal degradation of p53 in cervical cancer. |
| title_full | Crucial role of TSC-22 in preventing the proteasomal degradation of p53 in cervical cancer. |
| title_fullStr | Crucial role of TSC-22 in preventing the proteasomal degradation of p53 in cervical cancer. |
| title_full_unstemmed | Crucial role of TSC-22 in preventing the proteasomal degradation of p53 in cervical cancer. |
| title_short | Crucial role of TSC-22 in preventing the proteasomal degradation of p53 in cervical cancer. |
| title_sort | crucial role of tsc 22 in preventing the proteasomal degradation of p53 in cervical cancer |
| url | http://europepmc.org/articles/PMC3411576?pdf=render |
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