Tristetraprolin induces cell cycle arrest in breast tumor cells through targeting AP-1/c-Jun and NF-κB pathway
| Autor: | Li Xu, Jianguo Liu, William S. M. Wold, Weiguang Cui, Lin Wei, Gerald M. Wilson, Huan Ning, Ling Gu, Christina R. Ross, Baoling Ying, Qinghong Wang, Wenbao Lu, Hui Peng |
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| Rok vydání: | 2015 |
| Předmět: |
Time Factors
Cell cycle checkpoint Transcription Genetic Proto-Oncogene Proteins c-jun Tristetraprolin Breast Neoplasms Cell Cycle Proteins Transfection Mice breast cancer hemic and lymphatic diseases Animals Humans Medicine heterocyclic compounds Nuclear protein Cell Proliferation biology Cell growth business.industry c-jun apoptosis Transcription Factor RelA Nuclear Proteins Protein-Tyrosine Kinases respiratory system Cell cycle AP-1 Tumor Burden 3. Good health Gene Expression Regulation Neoplastic Transcription Factor AP-1 Wee1 HEK293 Cells Oncology S Phase Cell Cycle Checkpoints Cancer cell Immunology MCF-7 Cells Cancer research biology.protein Heterografts cell cycle Female business therapeutics Research Paper Signal Transduction |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | The main characteristic of cancers, including breast cancer, is the ability of cancer cells to proliferate uncontrollably. However, the underlying mechanisms of cancer cell proliferation, especially those regulated by the RNA binding protein tristetraprolin (TTP), are not completely understood. In this study, we found that TTP inhibits cell proliferation in vitro and suppresses tumor growth in vivo through inducing cell cycle arrest at the S phase. Our studies demonstrate that TTP inhibits c-Jun expression through the C-terminal Zn finger and therefore increases Wee1 expression, a regulatory molecule which controls cell cycle transition from the S to the G2 phase. In contrast to the well-known function of TTP in regulating mRNA stability, TTP inhibits c-Jun expression at the level of transcription by selectively blocking NF-κB p65 nuclear translocation. Reconstitution of NF-κB p65 completely abolishes the inhibition of c-Jun transcription by TTP. Moreover, reconstitution of c-Jun in TTP-expressing breast tumor cells diminishes Wee1 overexpression and promotes cell proliferation. Our results indicate that TTP suppresses c-Jun expression that results in Wee1 induction which causes cell cycle arrest at the S phase and inhibition of cell proliferation. Our study provides a new pathway for TTP function as a tumor suppressor which could be targeted in tumor treatment. |
| Databáze: | OpenAIRE |
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