The mechanism of cell cycle dependent proteasome-mediated CdvB degradation in Sulfolobus acidocaldarius

Protein degradation helps order events in the cell division cycle in eukaryotes, bacteria and archaea. This process is best understood in eukaryotes, where chromosome segregation and mitotic exit are triggered by APC/C and ubiquitin-regulated proteasome-dependent degradation of Securin and Cyclin B, respectively. Recent findings show that the archaeal proteasome also targets cellular substrates, including CdvB, for degradation in a cell cycle-dependent manner in Sulfolobus acidocaldarius - one of the closest experimentally tractable archaeal relatives of eukaryotes. Here, using CdvB as a model target protein to explore the mechanism of cyclic protein degradation, we identify the C-terminal broken winged helix of CdvB, which was previously shown to bind CdvA, as a domain that is sufficient to render a fusion protein unstable as cells transit from division phase to G1 phase. In parallel, we show that the rate of CdvB degradation accelerates during division, in part due to a cell cycle-dependent increase in the expression of the proteasome-activating nucleotidase (PAN), under the control of a cyclically expressed novel transcription factor, "CCTF1" (saci_0800), that can repress PAN expression. Taken together, our findings reveal the mechanisms by which archaea, despite lacking CDK/cyclin or APC/C proteins, regulate proteasome-mediated degradation to order events during cell division.