Figure 3.

Regulation of nuclear factor kappa B (NF‐κB) signaling by N‐myc downstream‐regulated gene 2 (NDRG2)/protein phosphatase 2A (PP2A) complex. A central signaling component of the non‐canonical pathway is NF‐κB‐inducing kinase (NIK) and the NDRG2/PP2A complex regulating the kinase activity of NIK by dephosphorylation reaction. Homeostatic activation of the NF‐κB signaling system is known to be important in the development of adult T‐cell leukemia/lymphoma (ATLL). The low expression of miR‐31 in ATLL cells, which is involved in the repression of NIK expression, leads to increase in NIK protein. In addition to this phenomenon, NIK is highly phosphorylated with high kinase activity due to low expression of NDRG2, and dysregulation of NDRG2/PP2A complex was found to be an important factor in activating the non‐canonical NF‐κB pathway. Moreover, the downregulation of NDRG2 expression also induces activation of the canonical NF‐κB pathway through activation of the IκB kinase (IKK) complex by constitutive activation of AKT, which is derived from the phosphorylation of PTEN caused by downregulation of NDRG2 in ATLL cells. ¹⁵ Therefore, NDRG2 is one of the important regulatory factors of the NF‐κB pathway. This figure has been adapted from reference 15 with permission