High impact information on DOA1

• Notably, Cdc48 can bind Otu1 and Ufd3 simultaneously, making a cooperation of both inhibitory mechanisms possible [1].
• We isolated the gene involved, termed UFD3, which encodes an 80 kDa protein containing tandem repeats of a motif that is present in many eukaryotic proteins and called the WD repeat [2].
• Both co-immunoprecipitation and two-hybrid assays demonstrated that Ufd3p is an in vivo ligand of Cdc48p, an essential ATPase required for the cell cycle progression and the fusion of endoplasmic reticulum membranes [2].
• In the absence of DOA1, damage-induced ubiquitination of PCNA does not occur [3].
• The data suggest that Doa1 is the major source of ubiquitin for the DNA damage response and that Doa1 also plays an additional essential and more specific role in the monoubiquitination of histone H2B [3].

Biological context of DOA1

• While searching for regulators of virulence attributes of the human-pathogenic fungus Candida albicans, a gene was identified similar to the genes encoding the mammalian phospholipase A2-activating protein (PLAP) and the Saccharomyces cerevisiae protein Doa1, which is known to play a key role during ubiquitin (Ub)-dependent protein degradation [4].
• Role of Doa1 in the Saccharomyces cerevisiae DNA damage response [3].
• Both zzz4-1 and a deletion of ZZZ4 confer resistance to all five of the agents tested, suggesting that signal transduction may be involved in the response of these cells to volatile anesthetics [5].
• Here, we describe Saccharomyces cerevisiae Doa1, which helps to control the damage response by channeling ubiquitin from the proteosomal degradation pathway into pathways that mediate altered DNA replication and chromatin modification [3].
• Identification of a novel 29-linked polyubiquitin binding protein, Ufd3, using polyubiquitin chain analogues [6].

Physical interactions of DOA1

• Herein, we demonstrate that Cdc48 interacts directly with the C-terminal PUL domain of Doa1 [7].

Regulatory relationships of DOA1

• Mutations in Doa1 that block Hse1 binding but not Ub binding do not alter Ub levels but do result in the missorting of the MVB cargo GFP-Cps1 [8].

Other interactions of DOA1

• DOA1 and CDC48 mutations are epistatic, suggesting that their interaction is physiologically relevant [7].
• These data suggest that DOA1 of C. albicans, like its orthologue in S. cerevisiae, is associated with Ub-mediated proteolysis and has multiple functions [4].
• They were identified as Ubp14, the yeast ortholog of Isopeptidase T, and Ufd3, a member of the ubiquitin-fusion degradation pathway with unknown function [6].

References