AIP2 Activators

AIP2, an E3 ubiquitin ligase, orchestrates ubiquitin-dependent degradation of target proteins involved in various cellular processes. The identified activators directly or indirectly enhance AIP2 activity through specific signaling pathways or biological processes. Leptomycin B, by inhibiting CRM1, prevents the nuclear export of AIP2, leading to increased nuclear accumulation and enhanced ubiquitin ligase activity for targeted degradation of nuclear substrates. Phorbol 12-myristate 13-acetate (PMA) activates protein kinase C (PKC), triggering the phosphorylation of AIP2 and thereby enhancing its ubiquitin ligase activity. MG-132, a proteasome inhibitor, indirectly enhances AIP2 activity by stabilizing ubiquitinated substrates, allowing AIP2 more time for substrate recognition and degradation. Etoposide induces DNA damage and activates the ATM/ATR signaling pathway, leading to increased phosphorylation of AIP2 and enhanced ubiquitin ligase activity.

A23187, a calcium ionophore, directly enhances AIP2 activity by activating the calcium/calmodulin-dependent protein kinase II (CaMKII) pathway. Roscovitine, a cyclin-dependent kinase (CDK) inhibitor, directly enhances AIP2 activity by inhibiting CDKs and promoting cell cycle arrest, leading to increased phosphorylation of AIP2. Bay 11-7082 and Bay 11-7821, inhibitors of NF-κB activation and IKK, respectively, directly enhance AIP2 activity by blocking the NF-κB signaling pathway. 5-Azacytidine, a DNA methyltransferase inhibitor, indirectly enhances AIP2 activity by demethylating its promoter region and increasing its expression. UCN-01, a Chk1 inhibitor, indirectly enhances AIP2 activity by inducing replication stress and activating the ATM/ATR signaling pathway. SGC-CBP30, a BET family inhibitor, directly enhances AIP2 activity by blocking BET protein binding to its promoter region, increasing AIP2 transcription. Hexamethylene bisacetamide (HMBA), a differentiation inducer, indirectly enhances AIP2 activity by promoting cell differentiation, leading to increased AIP2 levels. The comprehensive understanding of these activators provides insights into potential strategies for modulating AIP2 activity and contributes to unraveling the complexity of ubiquitin-dependent protein degradation in cellular processes.