Anti-KLHL21: Mouse KLHL21 Antibody

KLHL21 is a substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for efficient chromosome alignment and cytokinesis. The KLHL21 E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB. Ubiquitination of AURKB by BCR(KLHL21) E3 ubiquitin ligase complex may not lead to its degradation by the proteasome. Aurora B is a member of the CPC together with the inner centromere protein (INCENP), Borealin/Dasra B, and survivin. Aurora B kinase activity depends on association with its coactivator INCENP and on autophosphorylation of Thr232. Importantly, the CPC is also regulated at the level of subcellular localization. In early mitosis, it localizes to centromeres, where it regulates kinetochore assembly and function and thereby plays essential roles in chromosome alignment, segregation, and the spindle assembly checkpoint. After anaphase onset, the CPC accumulates at the spindle midzone and the midbody, where it ensures completion of cytokinesis.² Studies suggest a critical role for the ubiquitination of CPC components. Ubiquitination of survivin may trigger CPC binding to centromeres, whereas Cul3–KLHL9–KLHL13 E3 ligase–dependent ubiquitination of Aurora B may regulate recruitment of the CPC to the spindle midzone. Indeed, KLHL9 and KLHL13 bind Aurora B in vivo and in vitro, and Aurora B is ubiquitinated in a KLHL9- and KLHL13-dependent manner. In Xenopus laevis egg extracts, the AAA-ATPase p97 in complex with the cofactors Ufd1-Npl4 binds ubiquitinated Aurora B and may extract it from mitotic chromosomes. Therefore, it is possible that Cul3–KLHL9–KLHL13 ubiquitinates Aurora B, thereby promoting translocation of the CPC to the spindle midzone. KLHL21 and KLHL22 are other two novel regulators of mitosis. Unlike KLHL22, KLHL21 regulates CPC translocation at the onset of anaphase and is required for completion of cytokinesis. KLHL21 directly interacts with Aurora B and mediates ubiquitination of Aurora B in vitro. In contrast to KLHL9 and KLHL13, KLHL21 localizes to midzone microtubules during anaphase and targets Cul3 and Aurora B to this region. Thus, differential localization of distinct Cul3 complexes with KLHL9, KLHL13, and KLHL21 may target different pools of Aurora B during mitosis. KLHL21 may function as a specificity factor to ubiquitinate Aurora B on the midzone, whereas KLHL9 and KLHL13 may mainly target the cytoplasmic pool of Aurora B at this stage.³