Kelch-like Protein 21 (KLHL21) Targets IκB Kinase-ß to Regulate Nuclear Factor κ-Light Chain Enhancer of Activated B Cells (NF-κB) Signaling Negatively.

Activation of IKKß is the key step in canonical activation of NF-κB signaling. Extensive work has provided insight into the mechanisms underlying IKKß activation through the identification of context-specific regulators. However, the molecular processes responsible for its negative regulation are not completely understood. Here, we identified KLHL21, a member of the Kelch-like gene family, as a novel negative regulator of IKKß. The expression of KLHL21 was rapidly down-regulated in macrophages upon treatment with proinflammatory stimuli. Overexpression of KLHL21 inhibited the activation of IKKß and degradation of IκBα, whereas KLHL21 depletion via siRNA showed the opposite results. Coimmunoprecipitation assays revealed that KLHL21 specifically bound to the kinase domain of IKKß via its Kelch domains and that this interaction was gradually attenuated upon TNFα treatment. Furthermore, KLHL21 did not disrupt the interaction between IKKß and TAK1, TRAF2, or IκBα. Also, KLHL21 did not require its E3 ubiquitin ligase activity for IKKß inhibition. Our findings suggest that KLHL21 may exert its inhibitory function by binding to the kinase domain and sequestering the region from potential IKKß inducers. Taken together, our data clearly demonstrate that KLHL21 negatively regulates TNFα-activated NF-κB signaling via targeting IKKß, providing new insight into the mechanisms underlying NF-κB regulation in cells.

[Treatment of skeletal Class II adult patients with microscrew implant anchorage and multi-loop edgewise arch wire].

OBJECTIVE: To evaluate the effects and mechanisms of the microscrew implant anchorage (MIA) combined with multi-loop edgewise arch wire (MEAW) technique in the treatment of skeletal Class II adult patients. METHODS: Eleven adult patients with skeletal Class II high-angle malocclusions were treated with fixed appliances. The spaces were closed by the springs from the MIA to the hook on the archwire. The height of the hook and the direction of the force were different according to the intrusion and retraction of upper anterior teeth. In the finishing stage, MEAW technique and modified class II elastics (from the first loop of MEAW to the MIA) were used for final detailing. Cephalometric analysis was used to evaluate the effect after treatment. RESULTS: After treatment, the decrease of SNA, ANB and FMA were (2.86 +/- 1.05) degrees , (2.82 +/- 0.96) degrees and (2.95 +/- 1.35) degrees , respectively. The torque control of upper anterior teeth was good. The protrusion of lower incisors and the molar extrusion were avoided. The upper molars were moved distally by (3.00 +/- 2.19) mm. CONCLUSIONS: The treatment of adult patients with skeletal Class II high angle malocclusions with MIA and MEAW technique could not only improve the facial esthetics but also avoided the common side effects of traditional Class II elastics.