1. Nuclear retention of the lncRNA SNHG1 by doxorubicin attenuates hnRNPC–p53 protein interactions
- Author
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Xiaofei Zheng, Jiao Fan, Shanshan Liu, Baolei Tian, Hanjiang Fu, Ying-Hua Jin, and Yuan Shen
- Subjects
0301 basic medicine ,HNRNPC ,Apoptosis ,Biology ,Biochemistry ,Models, Biological ,RNA Transport ,03 medical and health sciences ,Cell Line, Tumor ,Genetics ,medicine ,Humans ,Doxorubicin ,Nucleotide Motifs ,Molecular Biology ,Cell Nucleus ,Protein Stability ,Heterogeneous-Nuclear Ribonucleoprotein Group C ,Scientific Reports ,RNA ,Subcellular localization ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,P53 protein ,Cancer research ,RNA, Long Noncoding ,Tumor Suppressor Protein p53 ,Carrier Proteins ,Nucleus ,Nucleolin ,medicine.drug ,Protein Binding - Abstract
The protein p53 plays a crucial role in the regulation of cellular responses to diverse stresses. Thus, a major priority in cell biology is to define the mechanisms that regulate p53 activity in response to stresses or maintain it at basal levels under normal conditions. Moreover, further investigation is required to establish whether RNA participates in regulating p539s interaction with other proteins. Here, by conducting systematic experiments, we discovered a p53 interactor—hnRNPC—that directly binds to p53, destabilizes it, and prevents its activation under normal conditions. Upon doxorubicin treatment, the lncRNA SNHG1 is retained in the nucleus through its binding with nucleolin and it competes with p53 for hnRNPC binding, which upregulates p53 levels and promotes p53‐dependent apoptosis by impairing hnRNPC regulation of p53 activity. Our results indicate that a balance between lncRNA SNHG1 and hnRNPC regulates p53 activity and p53‐dependent apoptosis upon doxorubicin treatment, and further indicate that a change in lncRNA subcellular localization under specific circumstances is biologically significant.
- Published
- 2017