BTB-Kelch Proteins and TAk1 Kinase N Immune Function



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BTB-kelch proteins are putative components of E3 ligases with a BTB domain at the N terminus and several kelch repeats at the C terminus. KLHL6 and mKELCH are two members of this family. Conditional ablation of Klhl6 in B cells resulted in mild developmental phenotypes in bone marrow precursors. The number of peripheral B cells was decreased by half, and responded defectively in germinal center formation after antigen stimulations. mKELCH is a novel protein cloned from hearts. Knocked-in LacZ expressed predominantly at muscles and several photosensitive organs. TAK1 is a member of MAPKKK. Deletion of TAK1 prevented the maturation of CD4+ or CD8+ single positive thymocytes, leading to reduction of T cells in peripheral tissues. Thymocytes lacking TAK1 failed to activate NF-κB and JNK, and were prone to apoptosis upon stimulation. All three mouse models have provided important evidences in elucidating biological functions for each protein in vivo.