Modeling the interplay between the HIF-1 and p53 pathways in hypoxia.
Both the hypoxia-inducible factor-1 (HIF-1) and tumor suppressor p53 are involved in the cellular response to hypoxia. How the two transcription factors interact to determine cell fates is less well understood. Here, we developed a network model to characterize crosstalk between the HIF-1 and p53 pathways, taking into account that HIF-1α and p53 are targeted for proteasomal degradation by Mdm2 and compete for binding to limiting co-activator p300. We reported the network dynamics under various hypoxic conditions and revealed how the stabilization and transcriptional activities of p53 and HIF-1α are modulated to determine the cell fate. We showed that both the transrepression and transactivation activities of p53 promote apoptosis induction. This work provides new insight into the mechanism for the cellular response to hypoxia.
National Laboratory of Solid State Microstructures and Department of Physics, Nanjing University, Nanjing 210093, China.|School of Physics and Electronic Engineering, Jiangsu Normal University, Xuzhou 221116, China.
Chun-Hong
CH
Zhou
Kuang Yaming Honors School, Nanjing University, Nanjing 210093, China.
Xiao-Peng
XP
Zhang
National Laboratory of Solid State Microstructures and Department of Physics, Nanjing University, Nanjing 210093, China.|Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China.
Feng
F
Liu
National Laboratory of Solid State Microstructures and Department of Physics, Nanjing University, Nanjing 210093, China.|Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China.
Wei
W
Wang
D017209:Apoptosis / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics; D008954:Models, Biological; D011485:Protein Binding; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D016283:Proto-Oncogene Proteins p21(ras)