- Title
- c-Myc inactivation of p53 through the pan-cancer lncRNA MILIP drives cancer pathogenesis
- Creator
- Feng, Yu Chen; Liu, Xiao Ying; Teng, Liu; Ji, Qiang; Wu, Yongyan; Li, Jin Ming; Gao, Wei; Zhang, Yuan Yuan; La, Ting; Tabatabaee, Hessam; Yan, Xu Guang; Jamaluddin, M. Fairuz B.; Zhang, Didi; Guo, Su Tang; Scott, Rodney J.; Liu, Tao; Thorne, Rick F.; Zhang, Xu Dong; Jin, Lei
- Relation
- Nature Communications Vol. 11, Issue 1, no. 4980
- Publisher Link
- http://dx.doi.org/10.1038/s41467-020-18735-8
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2020
- Description
- The functions of the proto-oncoprotein c-Myc and the tumor suppressor p53 in controlling cell survival and proliferation are inextricably linked as "Yin and Yang" partners in normal cells to maintain tissue homeostasis: c-Myc induces the expression of ARF tumor suppressor (p14ARF in human and p19ARF in mouse) that binds to and inhibits mouse double minute 2 homolog (MDM2) leading to p53 activation, whereas p53 suppresses c-Myc through a combination of mechanisms involving transcriptional inactivation and microRNA-mediated repression. Nonetheless, the regulatory interactions between c-Myc and p53 are not retained by cancer cells as is evident from the often-imbalanced expression of c-Myc over wildtype p53. Although p53 repression in cancer cells is frequently associated with the loss of ARF, we disclose here an alternate mechanism whereby c-Myc inactivates p53 through the actions of the c-Myc-Inducible Long noncoding RNA Inactivating P53 (MILIP). MILIP functions to promote p53 polyubiquitination and turnover by reducing p53 SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2). MILIP upregulation is observed amongst diverse cancer types and is shown to support cell survival, division and tumourigenicity. Thus our results uncover an inhibitory axis targeting p53 through a pan-cancer expressed RNA accomplice that links c-Myc to suppression of p53.
- Subject
- p53; cancer cells; c-Myc; cancer pathogenesis
- Identifier
- http://hdl.handle.net/1959.13/1421675
- Identifier
- uon:37757
- Identifier
- ISSN:2041-1723
- Rights
- Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2020.
- Language
- eng
- Full Text
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