Identification of a set of yeast genes coding for a novel family of putative ATPases with high similarity to constituents of the 26S protease complex

Abstract

There is accumulating evidence for a large, highly conserved gene family of putative ATPases. We have identified 12 different members of this novel gene family (the YTA family) in yeast and determined the nucleotide sequences of nine of these genes. All of the putative gene products are characterized by the presence of a highly conserved domain of 300 amino acids containing specialized forms of the A and B boxes of ATPases. YTA1, YTA2, YTA3 and YTA5 exhibit significant similarity to proteins involved in human immunodeficiency virus Tat-mediated gene expression but more significantly to subunits of the human 26S proteasome. YTA1 and YTA2 are essential genes in yeast. Remarkably, the cDNA of human TBP-1 can compensate for the loss of YTA1. Preliminary experiments indicate that YTA1 is a component of the 26S protease complex from yeast. Our findings lead us to propose that YTA1, YTA2, YTA3 and YTA5 function as regulatory subunits of the yeast 26S proteasome. YTA10, YTA11 and YTA12 share significant homology with the Escherichia coli FtsH protein, and together with YTA4 and YTA6 may constitute a separate subclass within this family of putative ATPases.

Knockout of caspase-like gene, YCA1 , abrogates apoptosis and elevates oxidized proteins in Saccharomyces cerevisiae

“…Moreover, oxidized proteins are retained by maternal cells so that daughter cells begin with a lower oxidized protein burden (36). There is considerable evidence that the 20S proteasome is responsible for the preferential degradation of oxidatively modified intracellular proteins in the absence of ATP and ubiquitin (22)(23)(24)(25)(26)(37)(38)(39), whereas the 26S proteasome (with or without ATP͞ubiquitin) has only a minimal ability to selectively degrade oxidatively modified proteins (37). In another report, it was demonstrated that the ATP͞ubiquitin-dependent 26S proteasome is very sensitive to direct oxidative inactivation (39), and the oxidative stress eventually suppresses the ubiquitinylation process (40), whereas the 20S proteasome complex is quite resistant (39).…”

The Saccharomyces cerevisiae OXA1 gene is required for the correct assembly of cytochrome c oxidase and oligomycin‐sensitive ATP synthase

“…Recently two genes, RCA1 and AFG3, were shown to control the assembly of more than one respiratory complex [21]. These genes belong to the AAA protein family and would code for ATP-dependent metallo-proteases required for the degradation of incompletely synthesized or misfolded polypeptides of the mitochondrial inner membrane [22][23][24][25][26][27][28]. The inactivation of RCAI or AFG3 was shown to diminish the NADH cytochrome c oxido-reductase, the cytochrome c oxidase and the ATPase activities, as well as to cause an arrest in assembly of the complexes IlI and IV and to delay the assembly of the F1-ATPase complex components [21,29].…”

Failure to Assemble the α3 β3 Subcomplex of the ATP Synthase Leads to Accumulation of the α and β Subunits within Inclusion Bodies and the Loss of Mitochondrial Cristae in Saccharomyces cerevisiae

“…Consistent with this idea, many subunits of these complexes are quickly degraded in mutants that fail to associate them with their partner subunits. Mitochondrial ATPdependent proteases involved in such degradative processes include Pim1p (33,34) in the matrix and two membraneembedded proteases, Yme1p and Afg3p/Rca1p, of the AAA family of ATPases (35)(36)(37)(38)(39). Pim1p has been implicated in the degradation of imported proteins that fail to fold into a native structure.…”