p31comet-Induced Cell Death Is Mediated by Binding and Inactivation of Mad2.

p31comet-Induced Cell Death Is Mediated by Binding and Inactivation of Mad2.

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Mad2, a key component of the spindle checkpoint, is closely associated with chromosomal instability and poor prognosis in cancer.p31comet is a Mad2-interacting protein that serves as a spindle checkpoint silencer at mitosis.In this study, we showed that p31comet-induced apoptosis and senescence occur via counteraction of Mad2 activity.Upon retroviral transduction of p31comet, the majority of human cancer cell lines tested sophie allport bee curtains lost the ability to form colonies in a low-density seeding assay.

Cancer cells with p31comet overexpression underwent distinct apoptosis and/or senescence, irrespective of p53 status, confirming the cytotoxicity of p31comet.Interestingly, both cytotoxic and Mad2 binding activities were eliminated upon deletion of the C-terminal 30 amino acids of p31comet.Point mutation or deletion of the region affecting Mad2 binding additionally abolished cytotoxic activity.Consistently, wild-type Mad2 interacting with p31comet, but not its non-binding mutant, inhibited cell death, indicating that the mechanism of p31comet-induced cell death involves Mad2 inactivation.

Our results clearly suggest that the regions of p31comet affecting interactions with kenya tree coral for sale Mad2, including the C-terminus, are essential for induction of cell death.The finding that p31comet-induced cell death is mediated by interactions with Mad2 that lead to its inactivation is potentially applicable in anticancer therapy.