The SCF ubiquitin ligase complex mediates degradation of the tumor suppressor FBXO31 and thereby prevents premature cellular senescence.

The tumor suppressor F-box protein 31 (FBXO31) is indispensable for maintaining genomic stability. Its levels drastically increase following DNA damage, leading to cyclin D1 and MDM2 degradation and G and G/M arrest. Prolonged arrest in these phases leads to cellular senescence.

Degradation of FBXO31 by APC/C is regulated by AKT- and ATM-mediated phosphorylation.

The F-box protein FBXO31 is a tumor suppressor that is encoded in 16q24.3, for which there is loss of heterozygosity in various solid tumors. FBXO31 serves as the substrate-recognition component of the SKP/Cullin/F-box protein class of E3 ubiquitin ligases and has been shown to direct degradation of pivotal cell-cycle regulatory proteins including cyclin D1 and the p53 antagonist MDM2.

FBXO32 activates NF-κB through IκBα degradation in inflammatory and genotoxic stress.

In response to diverse stresses, the canonical NF-κB pathway gets activated primarily to protect the cells and maintain their genomic integrity. It activates the cell cycle checkpoints allowing the cells with limited damage to restore a normal life cycle. One of the key events in activation of the canonical NF-κB pathway is the selective proteasomal degradation of IκBα.