MYC is in the CARDs: CBM complexes coordinate immune and MYC-dependent cellular function.

MYC is a transcription factor crucial for a host of cellular functions from proliferation to metabolism, and MYC dysregulation contributes to disease pathogenesis. A growing body of evidence suggests that MYC signaling is regulated by the caspase activation and recruitment domain-coiled-coil (CARD-CC) proteins: a family of immunological signaling mediators that canonically drive NF-κB signaling across nearly all tissues. MYC regulation coordinated by the CARD-CC proteins occurs by multiple mechanisms, including transcription, physical binding, and subcellular localization. Herein, we highlight the hallmark studies that collectively broaden the sphere of influence of CBM complexes beyond NF-κB to include MYC, which has functional impact on cells within and likely beyond the immune system. The studies reviewed herein provide rationale for future studies that examine non-canonical CBM-MYC signaling, its relationship with canonical NF-κB signaling, and its contribution to human health and disease.