The ubiquitin-proteasome system plays a crucial role in cell cycle progression. A previous study suggested that Spo12, a component of the Cdc14 early anaphase release (FEAR) network, is targeted for degradation by the APC/C complex in G1 phase. In the present study, we demonstrate that the Hect-type ubiquitin ligase Tom1 contributes to the turnover of Spo12 in G2/M phase. Coimmunoprecipitation analysis confirmed that Tom1 and Spo12 interact. Overexpression of Spo12 is cytotoxic in the absence of Tom1. Notably, Spo12 is degraded in S phase even in the absence of Tom1 and Cdh1, suggesting that an additional E3 ligase(s) also mediates Spo12 degradation. Together, we propose that several distinct degradation pathways control the level of Spo12 during the cell cycle.
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