Reversion of Temperature-Sensitive Mutation by Inhibition of Proteasome-Mediated Degradation of Mutated D123 Protein.

Okuda, Atsuyuki; Ohtsu, Masumi; Kimura, Genki

doi:10.1247/csf.26.205

Cited by 4 publications

(4 citation statements)

References 20 publications

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“…The mutant D123 protein has an Ala-109 3 Val alteration in sequence (32) and was reported to result in a polypeptide that is degraded at the restrictive temperature (33) in a lactacystinsensitive manner (34). The D123 gene is expressed in the cytosol of human and rat tissues, with expression in testis being highest (35).…”

Section: Cdc123 Is the Functional And Structural Homolog Of Mammalianmentioning

confidence: 99%

Cdc123 and Checkpoint Forkhead Associated with RING Proteins Control the Cell Cycle by Controlling eIF2γ Abundance

Bieganowski

Shilinski

Tsichlis

et al. 2004

Journal of Biological Chemistry

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Eukaryotic initiation factor 2 (eIF2) is a central regulator of translational initiation in times of growth and times of stress. Here we discovered three new conserved regulators of eIF2 in Saccharomyces cerevisiae. cdc123, homolog of mammalian D123, is a new cell division cycle mutant with a G 2 delay at permissive temperature and a terminal, mating-proficient G 1 arrest point. Cdc123 protein is regulated by nutrient availability. CHF1 and CHF2, homologs of mammalian checkpoint forkhead associated with RING genes, are required for G 2 delay and G 1 arrest of cdc123-4 and promote G 1 delay when overexpressed. Cell cycle delaying activity and the natural instability of Chf1 and Chf2 depend on the integrity of both domains and association with Cdc123. Genetic analysis maps the Chf1 forkhead associated domainbinding site to the conserved Thr-274 of Cdc123, suggesting that mammalian D123 is a key target of Chfr. Gcd11, the ␥ subunit of eIF2, is an additional Cdc123-interacting protein that is an essential target of the Cdc123 cell cycle promoting and Chf cell cycle arresting activity whose abundance is regulated by Cdc123, Chf1, and Chf2. Loss of cdc123 activity promotes Chf1 and Chf2 accumulation and Gcd11 depletion, accounting for the essentiality of Cdc123. The data establish the Cdc123-Chf-Gcd11 axis as an essential pathway for nutritional control of START that runs parallel to the Tor-Gcn2-Sui2 system of translational control.

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Section: Cdc123 Is the Functional And Structural Homolog Of Mammalianmentioning

confidence: 99%

Cdc123 and Checkpoint Forkhead Associated with RING Proteins Control the Cell Cycle by Controlling eIF2γ Abundance

Bieganowski

Shilinski

Tsichlis

et al. 2004

Journal of Biological Chemistry

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“…Yeast strains overexpressing CDC123 displayed a second, slightly larger isoform of CDC123 at low levels [ 46 ]. This isoform was suggested to result from an unknown modification to CDC123 and was linked to its proteasomal degradation [ 47 ]. The same work ruled out ubiquitin- and phosphoryl-group additions as potential modifications resulting in this isoform [ 47 ].…”

Section: Resultsmentioning

confidence: 99%

“…This isoform was suggested to result from an unknown modification to CDC123 and was linked to its proteasomal degradation [ 47 ]. The same work ruled out ubiquitin- and phosphoryl-group additions as potential modifications resulting in this isoform [ 47 ]. In light of the peptide-bond forming activity predicted for the R2K clade ATP-grasp proteins, we posit that the observed isoform perhaps results from automodification via serial ligation of amino acids to a particular sidechain or the C-terminus comparable to the modifications catalyzed by RimK on the ribosomal protein S6 or the TTLs on tubulins.…”

Section: Resultsmentioning

confidence: 99%

The eukaryotic translation initiation regulator CDC123 defines a divergent clade of ATP-grasp enzymes with a predicted role in novel protein modifications

2015

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Deciphering the origin of uniquely eukaryotic features of sub-cellular systems, such as the translation apparatus, is critical in reconstructing eukaryogenesis. One such feature is the highly conserved, but poorly understood, eukaryotic protein CDC123, which regulates the abundance of the eukaryotic translation initiation eIF2 complex and binds one of its components eIF2γ. We show that the eukaryotic protein CDC123 defines a novel clade of ATP-grasp enzymes distinguished from all other members of the superfamily by a RAGNYA domain with two conserved lysines (henceforth the R2K clade). Combining the available biochemical and genetic data on CDC123 with the inferred enzymatic function, we propose that the eukaryotic CDC123 proteins are likely to function as ATP-dependent protein-peptide ligases which modify proteins by ribosome-independent addition of an oligopeptide tag. We also show that the CDC123 family emerged first in bacteria where it appears to have diversified along with the two other families of the R2K clade. The bacterial CDC123 family members are of two distinct types, one found as part of type VI secretion systems which deliver polymorphic toxins and the other functioning as potential effectors delivered to amoeboid eukaryotic hosts. Representatives of the latter type have also been independently transferred to phylogenetically unrelated amoeboid eukaryotes and their nucleo-cytoplasmic large DNA viruses. Similarly, the two other prokaryotic R2K clade families are also proposed to participate in biological conflicts between bacteriophages and their hosts. These findings add further evidence to the recently proposed hypothesis that the horizontal transfer of enzymatic effectors from the bacterial endosymbionts of the stem eukaryotes played a fundamental role in the emergence of the characteristically eukaryotic regulatory systems and sub-cellular structures.ReviewersThis article was reviewed by Michael Galperin and Sandor Pongor.Electronic supplementary materialThe online version of this article (doi:10.1186/s13062-015-0053-x) contains supplementary material, which is available to authorized users.

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“…Therefore, CDC123 is essential for eIF2 assembly and cell viability. In rats, D123 A109V mutation results in temperature‐sensitive G1 arrest (Okuda et al ., , ). However, the underlying molecular mechanism is still not clear, although the gene was identified about two decades ago.…”

Section: Discussionmentioning

confidence: 99%

BICELLULAR POLLEN 1 is a modulator of DNA replication and pollen development in Arabidopsis

et al. 2018

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During male gametogenesis in Arabidopsis, the haploid microspore undergoes an asymmetric division to produce a vegetative and a generative cell, the latter of which continues to divide symmetrically to form two sperms. This simple system couples cell cycle with cell fate specification.Here we addressed the role of DNA replication in male gametogenesis using a mutant bicellular pollen 1 (bice1), which produces bicellular, rather than tricellular, pollen grains as in the wild-type plant at anthesis.The mutation prolonged DNA synthesis of the generative cell, which resulted in c. 40% of pollen grains arrested at the two-nucleate stage. The extended S phase did not impact the cell fate of the generative cell as shown by cell-specific markers. BICE1 encodes a plant homolog of human D123 protein that is required for G1 progression, but the underlying mechanism is unknown.Here we showed that BICE1 interacts with MCM4 and MCM7 of the pre-replication complex. Consistently, double mutations in BICE1 and MCM4, or MCM7, also led to bicellular pollen and condensed chromosomes. These suggest that BICE1 plays a role in modulating DNA replication via interaction with MCM4 and MCM7.

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Reversion of Temperature-Sensitive Mutation by Inhibition of Proteasome-Mediated Degradation of Mutated D123 Protein.

Cited by 4 publications

References 20 publications

Cdc123 and Checkpoint Forkhead Associated with RING Proteins Control the Cell Cycle by Controlling eIF2γ Abundance

Cdc123 and Checkpoint Forkhead Associated with RING Proteins Control the Cell Cycle by Controlling eIF2γ Abundance

The eukaryotic translation initiation regulator CDC123 defines a divergent clade of ATP-grasp enzymes with a predicted role in novel protein modifications

BICELLULAR POLLEN 1 is a modulator of DNA replication and pollen development in Arabidopsis

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