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p53 upregulates PLCε-IP3-Ca2+ pathway and inhibits autophagy through its target gene Rap2B
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Jiehui Di1,5,*, Juanjuan Tang1,4,*, Heya Qian1, Derek A. Franklin5, Chad Deisenroth5,6, Yoko Itahana5,7, Junnian Zheng1,2,3 and Yanping Zhang1,2,5
1 Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, P.R. China
2 Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, P.R. China
3 Center of Clinical Oncology and Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu, P.R. China
4 Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu, P.R. China
5 Department of Radiation Oncology and Lineberger Comprehensive Cancer Center, School of Medicine, the University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
6 The Hamner Institutes for Health Sciences, Institute for Chemical Safety Sciences, Research Triangle Park, NC, USA
7 Cancer & Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore
* These authors have contributed equally to this work
Junnian Zheng, email:
Yanping Zhang, email:
Keywords: p53, Rap2B, PLCε-IP3-Ca2+ pathway, autophagy
Received: March 22, 2017 Accepted: May 08, 2017 Published: May 23, 2017
The tumor suppressor p53 plays a pivotal role in numerous cellular responses as it regulates cell proliferation, metabolism, cellular growth, and autophagy. In order to identify novel p53 target genes, we utilized an unbiased microarray approach and identified Rap2B as a robust candidate, which belongs to the Ras-related GTP-binding protein superfamily and exhibits increased expression in various human cancers. We demonstrated that p53 increases the intracellular IP3 and Ca2+ levels and decreases the LC3 protein levels through its target gene Rap2B, suggesting that p53 can inhibit the autophagic response triggered by starvation via upregulation of the Rap2B-PLCε-IP3-Ca2+ pathway. As a confirmed target gene of p53, we believe that further investigating potential functions of Rap2B in autophagy and tumorigenesis will provide a novel strategy for cancer therapy.
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