Proteases and caspase-like activity in the yeast Saccharomyces cerevisiae

Abstract

A variety of proteases have been implicated in yeast PCD (programmed cell death) including the metacaspase Mca1 and the separase Esp1, the HtrA-like serine protease Nma111, the cathepsin-like serine carboxypeptideases and a range of vacuolar proteases. Proteasomal activity is also shown to have an important role in determining cell fate, with both pro- and anti-apoptotic roles. Caspase 3-, 6- and 8-like activities are detected upon stimulation of yeast PCD, but not all of this activity is associated with Mca1, implicating other proteases with caspase-like activity in the yeast cell death response. Global proteolytic events that accompany PCD are discussed alongside a consideration of the conservation of the death-related degradome (both at the level of substrate choice and cleavage site). The importance of both gain-of-function changes in the degradome as well as loss-of-function changes are highlighted. Better understanding of both death-related proteases and their substrates may facilitate the design of future antifungal drugs or the manipulation of industrial yeasts for commercial exploitation.

Proteome and metabolome profiling of wild-type and YCA1 -knock-out yeast cells during acetic acid-induced programmed cell death

“…With this respect yeast metacaspase-encoding gene YCA1 has been shown to be a positive regulator of yeast PCD induced by different stimuli [62], including acetic acid [13]. Yet, no apoptosome has been shown in yeast and a variety of proteases have been shown to participate in yeast PCD, not all of these activities being associated with YCA1 [6]. Importantly, we have previously shown and here confirmed that AA-PCD occurs both in WT and yca1 cells but with a lower death rate in the latter cells.…”

“…A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 6 Samples were analyzed using a split-free nano-flow liquid chromatography system (EASY-nLC II, …”

Mechanism of liponecrosis, a distinct mode of programmed cell death

“…51 It is involved in degrading various cytosolic proteins in about 40% of the numerous apoptotic PCD scenarios initiated in response to a variety of stimuli. [52][53][54] Yca1p can be activated by: (1) ROS and/or cytochrome c released from mitochondria into the cytosol; 49,53,55 and (2) Nma111p, a serine protease which in the nucleus degrades Bir1p, the only presently known inhibitor of Yca1p (Fig. 9A).…”

Programmed Cell Death Initiation and Execution in Budding Yeast

“…The genetic analyses possible in yeast will be able to address whether functional overlap exists between proteases, or whether additional proteases exist that have not been ascribed a role in PCD control. In support of the latter possibility, protease activities that do not correspond to known caspase-like enzymes have been identified that are able to cleave fluorescent substrates with specificities similar to mammalian caspases (Wilkinson and Ramsdale 2011).…”