KLHL22 Antibody - #DF13770

Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex required for chromosome alignment and localization of PLK1 at kinetochores. The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation. Monoubiquitination of PLK1 does not lead to PLK1 degradation. The BCR(KLHL22) ubiquitin ligase complex is also responsible for the amino acid-stimulated 'Lys-48' polyubiquitination and proteasomal degradation of DEPDC5. Through the degradation of DEPDC5, releases the GATOR1 complex-mediated inhibition of the TORC1 pathway. It is therefore an amino acid-dependent activator within the amino acid-sensing branch of the TORC1 pathway, indirectly regulating different cellular processes including cell growth and autophagy.

Cytoplasm>Cytosol. Cytoplasm>Cytoskeleton>Microtubule organizing center>Centrosome. Cytoplasm>Cytoskeleton>Spindle. Nucleus. Lysosome.
Note: Mainly cytoplasmic in prophase and prometaphase. Associates with the mitotic spindle as the cells reach chromosome bi-orientation. Localizes to the centrosomes shortly before cells enter anaphase After anaphase onset, predominantly associates with the polar microtubules connecting the 2 opposing centrosomes and gradually diffuses into the cytoplasm during telophase (PubMed:23455478). Localizes to the nucleus upon amino acid starvation (PubMed:29769719). Relocalizes to the cytosol and associates with lysosomes when amino acids are available (PubMed:29769719).

Component of the BCR(KLHL22) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL22 and RBX1. Interacts with PLK1. Interacts with DEPDC5 (via DEP domain); the interaction depends on amino acid availability. Interacts with YWHAE; required for the nuclear localization of KLHL22 upon amino acid starvation.