Type 2C protein phosphatases (PP2Cs) regulate cell proliferation in the yeast Saccharomyces cerevisiae

Regulation of cell proliferation is important for maintaining healthy and functional cellular homeostasis. Normal cells proliferate in the presence of growth factors, but when cells experience genomic instability and oxidative stress, cell cycle arrest is triggered, resulting in cellular senescence and ageing.

We identified the involvement of type 2 C protein phosphatases (PP2Cs) in the regulation of cell proliferation in budding yeast by cloning and expressing Ptc1-7, and measuring their proliferation using a 96-well microplate-based assay. Interestingly, loss of PP2C could also promote cell proliferation. Besides, mutations of Ptc4 at D48 or D83 or both could still promote cell proliferation and did not affect the cell proliferation regulated by Ptc4. Moreover, a proliferation assay using gene deletion strains reveals that Ptc4 is potentially involved in the regulation of Rim15, which is a key regulator of cell cycle arrest to promote cell proliferation.

We investigated the roles of PP2Cs in proliferation and discovered that its role in promoting cell proliferation activity is potentially by modulating Rim15, mediated through the regulation of the HOG or TORC1/Sch9 pathways. This study also highlights the challenge of investigating genes with isoforms as stochastic modulation mechanisms can allow cells to bypass their predetermined signal transduction network to adapt to cellular changes, giving rise to new phenotypes.