The tumor suppressor, p53, negatively regulates non-canonical NF-κB signaling through miRNA-induced silencing of NF-κB-inducing kinase

Cited 10 time in scopus
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Title
The tumor suppressor, p53, negatively regulates non-canonical NF-κB signaling through miRNA-induced silencing of NF-κB-inducing kinase
Author(s)
Hanbit Jang; Seulki Park; J Kim; Jong Hwan KimSeon-Young Kim; S Cho; Sung Goo ParkByoung Chul Park; Sunhong Kim; Jeong Hoon Kim
Bibliographic Citation
Molecules and Cells, vol. 43, no. 1, pp. 23-33
Publication Year
2020
Abstract
NF-κB signaling through both canonical and non-canonical pathways plays a central role in immune responses and inflammation. NF-κB-inducing kinase (NIK) stabilization is a key step in activation of the non-canonical pathway and its dysregulation implicated in various hematologic malignancies. The tumor suppressor, p53, is an established cellular gatekeeper of proliferation. Abnormalities of the TP53 gene have been detected in more than half of all human cancers. While the non-canonical NF-κB and p53 pathways have been explored for several decades, no studies to date have documented potential cross-talk between these two cancer-related mechanisms. Here, we demonstrate that p53 negatively regulates NIK in an miRNA-dependent manner. Overexpression of p53 decreased the levels of NIK, leading to inhibition of the non-canonical NF-κB pathway. Conversely, its knockdown led to increased levels of NIK, IKKα phosphorylation, and p100 processing. Additionally, miR-34b induced by nutlin-3 directly targeted the coding sequences (CDS) of NIK. Treatment with anti-miR-34b-5p augmented NIK levels and subsequent non-canonical NF-κB signaling. Our collective findings support a novel cross-talk mechanism between non-canonical NF-κB and p53.
Keyword
NF-κBinducing kinaseNF-κBcancermicroRNAp53tumor suppressor gene
ISSN
1016-8478
Publisher
Korea Soc-Assoc-Inst
DOI
http://dx.doi.org/10.14348/molcells.2019.0239
Type
Article
Appears in Collections:
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
Critical Diseases Diagnostics Convergence Research Center > 1. Journal Articles
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