FKBP51 employs both scaffold and isomerase functions to promote NF-κB activation in melanoma

摘要: Melanoma is the most aggressive skin cancer; its prognosis, particularly in advanced stages, disappointing largely due to resistance conventional anticancer treatments and high metastatic potential. NF-κB constitutive activation a major factor for apoptosis of melanoma. Several studies suggest role immunophilin FKBP51 activation, but underlying mechanism still unknown. In present study, we demonstrate that physically interacts with IKK subunits, facilitates complex assembly. FKBP51-knockdown inhibits binding IKKγ catalytic IKK-α -β, attenuates activity. Using FK506, an inhibitor isomerase activity, found IKK-regulatory involves both scaffold function Moreover, also TRAF2, upstream mediator activation. Interestingly, TPR PPIase domains are required interaction TRAF2 IKKγ, whereas only domain involved interactions IKKα β. Collectively, these results promotes by serving as well isomerase. Our findings have profound implications designing novel melanoma therapies based on modulation FKBP51.