Coordinated regulation of p31Cometand Mad2 expression is required for cellular proliferation

Abstract

p31Comet is a well-known interacting partner of the spindle assembly checkpoint (SAC) effector molecule Mad2. At the molecular level it is well established that p31Comet promotes efficient mitotic exit, specifically the metaphase-anaphase transition, by antagonizing Mad2 function. However, there is little knowledge of how p31Comet is regulated or the physiological importance of controlling p31Comet. Here, we show that the Rb-E2F pathway regulates p31Comet expression. In multiple tumor types (including breast and lung) p31Comet expression is increased along with Mad2. Expression of this antagonist-target pair is coordinated in cells and correlated in cancer. Moreover, a narrow range of p31Comet:Mad2 ratios is compatible with cellular viability. Our data suggest that coordinate regulation is important for the outgrowth of oncogenic cell populations. Our findings suggest that altered p31Comet:Mad2 expression ratios may provide new insight into altered SAC function and the generation of chromosomal instability in tumors. © 2013 Landes Bioscience.