Heritable activity: a prion that propagates by covalent autoactivation

Abstract

Known prions (infectious proteins) are self-propagating amyloids or conformationally altered proteins, but in theory an enzyme necessary for its own activation could also be a prion (or a gene composed of protein). We show that yeast protease B is such a prion, called [beta].[beta] is infectious, reversibly curable, and its de novo generation is induced by overexpression of the pro-protease. Present in normal cells but masked by the functionally redundant protease A, [beta] is advantageous during starvation and necessary for sporulation. We propose that other enzymes whose active, modified, form is necessary for their maturation might also be prions.

Transgenerational Epigenetic Inheritance: Prevalence, Mechanisms, and Implications for the Study of Heredity and Evolution

“…An example is the enzyme vacuolar protease B of Saccharomyces cerevisiae, whose active form is necessary for its own conversion from an inactive precursor to an active state. On glycerol media, where the precursor is synthesized in high amounts, the self-processing of the enzyme is indefinitely self-sustaining (Roberts and Wickner 2003). As noted by Wickner et al (2004), it is likely that other protein-modifying proteins may also directly or indirectly affect their own modification and behave as selfsustaining, cell-transmissible loops.…”

Non-Mendelian determinant [ ISP + ] in yeast is a nuclear-residing prion form of the global transcriptional regulator Sfp1

“…They correspond to amyloid forms of Swi1, Mca1, Cyc8, and Mot3 proteins, respectively. Besides these amyloid-based prions, two self-perpetuating determinants of nonamyloid nature, [β] and [GAR + ], were recently described (6,7). Thus, it is evident that protein inheritance is a widespread phenomenon, at least in lower eukaryotes.…”

Prion Variants and Species Barriers Among Saccharomyces Ure2 Proteins

“…Most dramatically, although centuries of human exposure to sheep scrapie has not produced detectable infection, the bovine spongiform encephalopathy (BSE) epidemic led to .200 cases of a variant of Creutzfeldt-Jakob disease (vCJD). That this difference is due to prion variant differences is shown by studies with transgenic mice (reviewed in Collinge and Clarke 2007 [b], which are prions of Ure2p, Sup35p, Rnq1p, Swi1p, and Prb1p, respectively (Wickner 1994;Derkatch et al 2001;Roberts and Wickner 2003;Du et al 2008). Ure2p is a regulator of nitrogen catabolism, repressing the genes encoding enzymes and transporters needed for the utilization of poor nitrogen sources (e.g., allantoate) specifically when a good nitrogen source (e.g., ammonia) is available (Cooper 2002).…”