Phenylbutyric acid induces the cellular senescence through an Akt/p21WAF1 signaling pathway
| Autor: | Chang-Young Jang, Jeong Min Choe, Joon Kim, Jeongwon Sohn, Hag Dong Kim |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Protein Folding endocrine system Biophysics Protein Serine-Threonine Kinases Biology Biochemistry eIF-2 Kinase Downregulation and upregulation Cell Line Tumor Endoribonucleases Humans Molecular Biology Protein kinase B Cellular Senescence PI3K/AKT/mTOR pathway Gene knockdown ATF6 Membrane Proteins Cell Biology Phenylbutyrates Activating Transcription Factor 6 Cell biology Unfolded Protein Response Unfolded protein response Signal transduction Chemical chaperone Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Biochemical and Biophysical Research Communications. 422:213-218 |
| ISSN: | 0006-291X |
| Popis: | Highlights: Black-Right-Pointing-Pointer Phenylbutyric acid induces cellular senescence. Black-Right-Pointing-Pointer Phenylbutyric acid activates Akt kinase. Black-Right-Pointing-Pointer The knockdown of PERK also can induce cellular senescence. Black-Right-Pointing-Pointer Akt/p21{sup WAF1} pathway activates in PERK knockdown induced cellular senescence. -- Abstract: It has been well known that three sentinel proteins - PERK, ATF6 and IRE1 - initiate the unfolded protein response (UPR) in the presence of misfolded or unfolded proteins in the ER. Recent studies have demonstrated that upregulation of UPR in cancer cells is required to survive and proliferate. Here, we showed that long exposure to 4-phenylbutyric acid (PBA), a chemical chaperone that can reduce retention of unfolded and misfolded proteins in ER, induced cellular senescence in cancer cells such as MCF7 and HT1080. In addition, we found that treatment with PBA activates Akt, which results in p21{sup WAF1} induction. Interestingly, the depletion of PERK but not ATF6 and IRE1 also induces cellular senescence, which was rescued by additional depletion of Akt. This suggests that Akt pathway is downstream of PERK in PBA induced cellular senescence. Taken together, these results show that PBA induces cellular senescence via activation of the Akt/p21{sup WAF1} pathway by PERK inhibition. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect