TY - JOUR
T1 - The protein level and transcription activity of activating transcription factor 1 is regulated by prolyl isomerase pin1 in nasopharyngeal carcinoma progression
AU - Huang, Guo Liang
AU - Liao, Dan
AU - Chen, Hua
AU - Lu, Yan
AU - Chen, Liyong
AU - Li, Huahui
AU - Li, Binbin
AU - Liu, Weilong
AU - Ye, Caiguo
AU - Li, Tong
AU - Zhu, Zhu
AU - Wang, Jian
AU - Uchida, Takafumi
AU - Zou, Ying
AU - Dong, Zigang
AU - He, Zhiwei
N1 - Funding Information:
Acknowledgements. This work was supported by National Natural Science Foundation of China (no: 81372137 and no: 30973374 to ZH; no: 81102048 to G-LH; no: 81502411 to BL) and Training Plan for Outstanding Young Teachers in Higher Education Institutions of Guangdong Province (no: YQ201403/YQ2014086 to G-LH). The authors thank Dr. Xiao-bin Lv in Nanchang University for his comments in the manuscript.
Funding Information:
This work was supported by National Natural Science Foundation of China (no: 81372137 and no: 30973374 to ZH; no: 81102048 to G-LH; no: 81502411 to BL) and Training Plan for Outstanding Young Teachers in Higher Education Institutions of Guangdong Province (no: YQ201403/YQ2014086 to G-LH). The authors thank Dr. Xiao-bin Lv in Nanchang University for his comments in the manuscript.
Publisher Copyright:
© The Author(s) 2016.
PY - 2016
Y1 - 2016
N2 - The function of activating transcription factor 1 (ATF1) and the mechanism about why ATF1 was over-phosphorylated in nasopharyngeal carcinoma (NPC) progression is completely undiscovered. In this study, a series of experiments both in vitro and in vivo were used to characterize a promotive function of ATF1 in NPC tumorigenesis and identify prolyl isomerase Pin1 as a novel regulator of ATF1 at post-transcription. First, we found that overexpression of ATF1 promoted colony formation in NPC. However, the high protein level of ATF1 in NPC was not resulted from high mRNA level. Then, a direct interaction between Pin1 and ATF1 at Thr184 was demonstrated using mammalian two-hybrid assay and coimmunoprecipitation. Cycloheximide (CHX) treatment indicated Pin1 stabilized the expression of ATF1 at post-transcription level. We confirmed that Pin1 upregulated ATF1 transcriptional activity of Bcl-2 using luciferase reporter assay, quantitative RT-PCR and western blot. Furthermore, the newly identified phosphorylation of ATF1 at Thr184 was suggested to have an important role in ATF1 function of transcription and tumor promotion. Finally, high expression of Pin1 in NPC tissue was found to be positively correlated with ATF1. The ATF1 promoted NPC tumorigenesis was regulated by Pin1 both in vitro and in vivo. All these findings clearly state that Pin1 is a novel regulator of ATF1 at Thr184 and thereby enhances ATF1 transcription activity and tumorigenesis promotive function in NPC.
AB - The function of activating transcription factor 1 (ATF1) and the mechanism about why ATF1 was over-phosphorylated in nasopharyngeal carcinoma (NPC) progression is completely undiscovered. In this study, a series of experiments both in vitro and in vivo were used to characterize a promotive function of ATF1 in NPC tumorigenesis and identify prolyl isomerase Pin1 as a novel regulator of ATF1 at post-transcription. First, we found that overexpression of ATF1 promoted colony formation in NPC. However, the high protein level of ATF1 in NPC was not resulted from high mRNA level. Then, a direct interaction between Pin1 and ATF1 at Thr184 was demonstrated using mammalian two-hybrid assay and coimmunoprecipitation. Cycloheximide (CHX) treatment indicated Pin1 stabilized the expression of ATF1 at post-transcription level. We confirmed that Pin1 upregulated ATF1 transcriptional activity of Bcl-2 using luciferase reporter assay, quantitative RT-PCR and western blot. Furthermore, the newly identified phosphorylation of ATF1 at Thr184 was suggested to have an important role in ATF1 function of transcription and tumor promotion. Finally, high expression of Pin1 in NPC tissue was found to be positively correlated with ATF1. The ATF1 promoted NPC tumorigenesis was regulated by Pin1 both in vitro and in vivo. All these findings clearly state that Pin1 is a novel regulator of ATF1 at Thr184 and thereby enhances ATF1 transcription activity and tumorigenesis promotive function in NPC.
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U2 - 10.1038/cddis.2016.349
DO - 10.1038/cddis.2016.349
M3 - Article
C2 - 28032861
AN - SCOPUS:85026465502
VL - 7
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
IS - 12
M1 - e2571
ER -