2. Academic Validation
  3. The protein level and transcription activity of activating transcription factor 1 is regulated by prolyl isomerase Pin1 in nasopharyngeal carcinoma progression

The protein level and transcription activity of activating transcription factor 1 is regulated by prolyl isomerase Pin1 in nasopharyngeal carcinoma progression

  • Cell Death Dis. 2016 Dec 29;7(12):e2571. doi: 10.1038/cddis.2016.349.
Guo-Liang Huang 1 2,  Dan Liao 1 2 3,  Hua Chen 1 2,  Yan Lu 1 2 4,  Liyong Chen 1 2,  Huahui Li 1 2,  Binbin Li 1 2,  Weilong Liu 5,  Caiguo Ye 1 2,  Tong Li 1 2,  Zhu Zhu 1 2,  Jian Wang 1 2,  Takafumi Uchida 6,  Ying Zou 1 2,  Zigang Dong 7,  Zhiwei He 1 2
Affiliations

Affiliations

  • 1 China-American Cancer Research Institute, Dongguan Scientific Research Center, Guangdong Medical University, Dongguan, China.
  • 2 Key Laboratory for Epigenetics of Dongguan City, Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan, China.
  • 3 Department of Gynaecology and Obstetrics, Dongguan Third People's Hospital, Affiliated Dongguan Shilong People's Hospital of Southern Medical University, Dongguan, China.
  • 4 Research Institute of Clinical Medicine, The First People's Hospital of Shunde Affiliate to Southern Medical University, Foshan, China.
  • 5 Experimental Animal Center, Shenzhen Third People's Hospital, Shenzhen, China.
  • 6 Department of Molecular Cell Biology, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi, Japan.
  • 7 The Hormel Institute, University of Minnesota, Austin, MN, USA.
PMID: 28032861 DOI: 10.1038/cddis.2016.349
Abstract

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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