Phosphorylation regulates the p 31 Comet – Mitotic Arrest Deficient 2 ( Mad 2 ) interaction to promote Spindle
نویسندگان
چکیده
The spindle assembly checkpoint (SAC) ensures the faithful segregation of the genome during mitosis by ensuring that sister chromosomes form bipolar attachments with microtubules of the mitotic spindle. p31 is an antagonist of the SAC effector Mad2 and promotes silencing of the SAC and mitotic progression. However, p31 interacts with Mad2 throughout the cell cycle. We show that p31 binds Mad2 solely in an inhibitory manner. We demonstrate that attenuating the affinity of p31 for Mad2 by phosphorylation promotes SAC activity in mitosis. Specifically, phosphorylation of S102 weakens p31-Mad2 binding and enhances p31-mediated bypass of the SAC. Our results provide the first evidence for regulation of p31 and demonstrate a previously unknown event controlling SAC activity.
منابع مشابه
Design of potent and selective hybrid inhibitors of the mitotic kinase Nek2: SAR, structural biology and cellular activity
We report herein a series of Nek2 inhibitors based on an aminopyridine scaffold. These compounds have been designed by combining key elements of two previously discovered chemical series. Structure based design led to aminopyridine (R)-21, a potent and selective inhibitor able to modulate Nek2 activity in cells. Introduction (Never in mitosis gene a)-related kinase-2 (Nek2) is a serine/threonin...
متن کاملP31comet, a member of the synaptonemal complex, participates in meiotic DSB formation in rice.
The human mitotic arrest-deficient 2 (Mad2) binding protein p31(comet) participates in the spindle checkpoint and coordinates cell cycle events in mitosis although its function in meiosis remains unknown in all organisms. Here, we reveal P31(comet) as a synaptonemal complex (SC) protein in rice (Oryza sativa L.). In p31(comet), homologous pairing and synapsis are eliminated, leading to the homo...
متن کاملp31comet acts to ensure timely spindle checkpoint silencing subsequent to kinetochore attachment
The spindle assembly checkpoint links the onset of anaphase to completion of chromosome-microtubule attachment and is mediated by the binding of Mad and Bub proteins to kinetochores of unattached or maloriented chromosomes. Mad2 and BubR1 traffic between kinetochores and the cytosol, thereby transmitting a "wait anaphase" signal to the anaphase-promoting complex. It is generally assumed that th...
متن کاملMadlp, a Phosphoprotein Component of the Spindle Assembly Checkpoint in Budding Yeast
The spindle assembly checkpoint prevents cells from initiating anaphase until the spindle has been fully assembled. We previously isolated mitotic arrest deficient (mad) mutants that inactivate this checkpoint and thus increase the sensitivity of ceils to benomyl, a drug that interferes with mitotic spindle assembly by depolymerizing microtubules. We have cloned the MAD1 gene and show that when...
متن کاملThe Bub2-dependent mitotic pathway in yeast acts every cell cycle and regulates cytokinesis.
In eukaryotes an abnormal spindle activates a conserved checkpoint consisting of the MAD and BUB genes that results in mitotic arrest at metaphase. Recently, we and others identified a novel Bub2-dependent branch to this checkpoint that blocks mitotic exit. This cell-cycle arrest depends upon inhibition of the G-protein Tem1 that appears to be regulated by Bfa1/Bub2, a two-component GTPase-acti...
متن کامل