c-Myc inactivation of p53 through the pan-cancer lncRNA MILIP drives cancer pathogenesis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-10-05

AUTHORS

Yu Chen Feng, Xiao Ying Liu, Liu Teng, Qiang Ji, Yongyan Wu, Jin Ming Li, Wei Gao, Yuan Yuan Zhang, Ting La, Hessam Tabatabaee, Xu Guang Yan, M. Fairuz B. Jamaluddin, Didi Zhang, Su Tang Guo, Rodney J. Scott, Tao Liu, Rick F. Thorne, Xu Dong Zhang, Lei Jin

ABSTRACT

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. More... »

PAGES

4980

Journal

TITLE

Nature Communications

ISSUE

1

VOLUME

11

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-020-18735-8

DOI

http://dx.doi.org/10.1038/s41467-020-18735-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1131425856

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/33020477


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