Skip to Content
Merck
  • The Tumor Suppressor, p53, Negatively Regulates Non-Canonical NF-κB Signaling through miRNAInduced Silencing of NF-κB-Inducing Kinase.

The Tumor Suppressor, p53, Negatively Regulates Non-Canonical NF-κB Signaling through miRNAInduced Silencing of NF-κB-Inducing Kinase.

Molecules and cells (2019-12-25)
Hanbit Jang, Seulki Park, Jaehoon Kim, Jong Hwan Kim, Seon-Young Kim, Sayeon Cho, Sung Goo Park, Byoung Chul Park, Sunhong Kim, Jeong-Hoon Kim
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-p62 (Sequestosome-1) Antibody, clone 11C9.2, clone 11C9.2, from mouse
Sigma-Aldrich
MISSION® shRNA, Purified DNA
Supelco
EPA 8260A Surrogate Standards Mix, certified reference material, 2000 μg/mL each component in methanol
Sigma-Aldrich
Monoclonal ANTI-FLAG® M2 antibody produced in mouse, 1 mg/mL, clone M2, affinity isolated antibody, buffered aqueous solution (50% glycerol, 10 mM sodium phosphate, and 150 mM NaCl, pH 7.4)
Sigma-Aldrich
Chloroquine diphosphate salt, powder or crystals, 98.5-101.0% (EP)
Sigma-Aldrich
3-Methyladenine, autophagy inhibitor
Supelco
Boron Standard for ICP, TraceCERT®, 10 g/L B in H2O (with <0.5% ammonium hydroxide nominal concentration)
Sigma-Aldrich
Bafilomycin A1 from Streptomyces griseus, ≥90% (HPLC)
Sigma-Aldrich
Monoclonal Anti-α-Tubulin antibody produced in mouse, ascites fluid, clone B-5-1-2
Sigma-Aldrich
Z-Leu-Leu-Leu-al, ≥90% (HPLC)