Coordinated regulation of p31^Comet and Mad2 expression is required for cellular proliferation

Abstract

p31^Comet is a well-known interacting partner of the spindle assembly checkpoint (SAC) effector molecule Mad2. At the molecular level it is well established that p31^Comet promotes efficient mitotic exit, specifically the metaphase–anaphase transition, by antagonizing Mad2 function. However, there is little knowledge of how p31^Comet is regulated or the physiological importance of controlling p31^Comet. Here, we show that the Rb–E2F pathway regulates p31^Comet expression. In multiple tumor types (including breast and lung) p31^Comet 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 p31^Comet: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 p31^Comet:Mad2 expression ratios may provide new insight into altered SAC function and the generation of chromosomal instability in tumors.

Keywords::

• cancer
• cell cycle
• spindle assembly checkpoint
• E2F
• Rb
• Mad2
• p31^Comet