Analysis of NF-𝜿B Pathway Proteins in Pediatric Hodgkin Lymphoma: Correlations with EBV Status and Clinical Outcome—A Children's Oncology Group Study

Figure 1

Classical and alternative NF-𝜅B pathway activation. (a) Activation of the classical NF-𝜅B pathway. Several receptors, including CD30, CD40, and LMP1, induce the classical NF-𝜅B pathway by activating the IKK complex. Phosphorylated IKK-𝛽 phosphorylates I𝜅B-𝛼, inducing I𝜅B polyubiquitination and degradation by the 26S proteasome. Following I𝜅B degradation, NF-𝜅B dimerizes with NF-𝜅B1/p50 and translocates into the nucleus where gene transcription is activated. (b) Activation of the alternative NF-𝜅B pathway. The alternative NF-𝜅B pathway is activated by a restricted set of cell-surface receptors, including CD30, CD40, and the BAFF receptor. Alternative NF-𝜅B pathway activation increases the stability of NIK, which phosphorylates and activates IKK-𝛼. IKK-𝛼 directly phosphorylates NF-𝜅B2/p100, inducing partial proteolysis of p100 to p52 by the 26S proteasome. The p52 NF-𝜅B subunit dimerizes with Rel-B and translocates into the nucleus, activating gene transcription. Proteins outlined in black were examined in the TMA. Cylindrical structure represents the 26S proteasome.

(a) Classical   NF-𝜅B activation pathway

(b) Alternative   NF-𝜅B activation pathway