Protein kinase C-driven nuclear factor kappa B signaling node (PKC-NF-κB node)

The Protein kinase C (PKC)-driven nuclear factor kappa B (NF-κB) signaling node is a critical intracellular pathway that translates extracellular signals, particularly from the B-cell receptor (BCR) and T-cell receptor (TCR), into gene expression programs governing cell survival and proliferation [1, 4]. This node centers on the activation of PKC isoforms (such as PKCβ in B cells and PKCθ in T cells), which subsequently trigger the assembly of the CBM signalosome—a complex comprising CARD11, BCL10, and MALT1 [3]. The CBM complex activates the IκB kinase (IKK) complex, leading to the phosphorylation and degradation of IκB proteins and the subsequent nuclear translocation of NF-κB transcription factors [3]. In many B-cell malignancies, such as the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL), this node is constitutively active due to oncogenic mutations in upstream components like CD79A/B or CARD11 itself [1, 2]. Pharmacological targeting of this node primarily involves PKC inhibitors like sotrastaurin or enzastaurin, as well as emerging MALT1 protease inhibitors, which aim to disrupt the survival signals in addicted tumor cells [2]. However, therapeutic intervention is complicated by the broad physiological necessity of NF-κB signaling in normal immune function, raising concerns about potential immunosuppression and off-target effects [2, 4].

Other names

PKC-NF-kappaB axisCBM complex signaling pathwayPKC-mediated NF-kappaB activationPKC-CARD11-BCL10-MALT1 axis

Inhibition of PKC isoforms (such as PKC-beta or PKC-theta) or downstream components like MALT1 to prevent the assembly of the CBM complex and subsequent NF-kappaB nuclear translocation.