Novel E3 ligase component FBXL7 ubiquitinates and degrades Aurora A, causing mitotic arrest

The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial Function by Mediating the Ubiquitylation and Proteasomal Degradation of Survivin

“…Modulates Mitochondrial Function-As we reported previously (20), ectopically expressed Fbxl7 induces apoptosis in cells. To further decode the underlying mechanism, we tested whether Fbxl7 affected mitochondrial function.…”

“…We have reported previously that the F-box protein Fbxl7 possesses proapoptotic activity and that it targets the mitotic kinase Aurora A for polyubiquitylation and degradation (20). Survivin, similar to Aurora A, has multiple functions, including inhibiting apoptosis and regulating mitosis.…”

“…A recently characterized F-box protein, Fbxl7 has been shown to regulate mitosis through targeting Aurora A kinase for polyubiquitylation and proteasomal degradation, which plays vital roles in mitotic spindle formation and chromosome segregation (20). Our previous studies have demonstrated that Fbxl7 displays proapoptotic activity (20,21). However, the nature of the molecular target for this F-box protein remained obscure.…”

“…Identifying the interaction between an F-box protein and its substrates has led to an improved understanding of how SCF E3 ligases mediate multiple biological functions, including gene expression, mitotic cell cycle progression, and inflammation. A recently characterized F-box protein, Fbxl7 has been shown to regulate mitosis through targeting Aurora A kinase for polyubiquitylation and proteasomal degradation, which plays vital roles in mitotic spindle formation and chromosome segregation (20). Our previous studies have demonstrated that Fbxl7 displays proapoptotic activity (20,21).…”

Calmodulin protects Aurora B on the midbody to regulate the fidelity of cytokinesis

“…[24][25][26][27][28][29] The SCF complex contains a catalytic core consisting of Skp1, Cullin1, the E2 ubiquitin-conjugating (Ubc) enzyme and a F box component that acts as a receptor targeting numerous substrates via phosphodegron elicited interactions. [30][31][32][33] The observation that Skp1 interacts with centromere-associated protein E (CENP-E) at the midbody suggests that SCF-based ligase complexes might regulate cytokinesis-associated proteins, although identification of an F-box protein targeting the midbody has not been demonstrated.…”