During the maternal-to-zygotic transition (MZT), maternal proteins in oocytes are degraded by the ubiquitin-proteasome system (UPS), which is first event after fertilization, and new proteins are then synthesized from the zygotic genome. Although degradation of accumulated maternal protein is essential for normal early embryonic development, the specific mechanisms underlying the UPS at the MZT are not well understood. We recently provided evidence that proteasomal degradation of maternal proteins is important for the onset of zygotic gene activation (ZGA), and that the zygote-specific proteasome assembly chaperone (ZPAC) plays an important role in the degradation of maternal proteins during mouse MZT. Here, we review why the degradation of maternal proteins via UPS is essential for embryonic reprogramming of the oocyte into a totipotent zygote that is makes somatic development possible.