Disease relevance of GRX4

• A novel monothiol glutaredoxin (Grx4) from Escherichia coli can serve as a substrate for thioredoxin reductase [1].

High impact information on GRX4

• In this work, another subfamily of yeast glutaredoxins (Grx3, Grx4, and Grx5) that differs from the first in containing a single cysteine residue at the putative active site is described [2].
• Thus, Grx3 and Grx4 are novel components required for Aft1 iron regulation that most likely occurs in the nucleus [3].
• Grx3 and Grx4 interact with Aft1 as shown by two-hybrid interactions and co-immunoprecipitation assays [3].
• Experiments with gene knock-out techniques showed that the reading frame encoding Grx4 was essential [1].
• Grx4 in reduced form contained three thiols, and treatment with oxidized GSH resulted in glutathionylation and formation of a disulfide [1].

Chemical compound and disease context of GRX4

• Remarkably, this disulfide of Grx4 was a direct substrate for NADPH and E. coli thioredoxin reductase, whereas the mixed disulfide was reduced by Grx1 [1].

Biological context of GRX4

• However, our results also suggest that Grx3 and Grx4 might play additional roles in the oxidative stress response through proteins other than Aft1 [4].
• The absence of both Grx3 and Grx4 induced a clear enrichment of G1 cells in asynchronous cultures, a slow growth phenotype, the accumulation of intracellular iron and a constitutive activation of the genes regulated by Aft1 [4].

Anatomical context of GRX4

• Fluorescence microscopy revealed that Grx3 is targeted to nuclear rim and endoplasmic reticulum, Grx4 primarily to the nucleus, and Grx5 to mitochondria [5].
• Grx5 is involved in iron/sulfur cluster assembly at the mitochondria, but the function of Grx3 and Grx4 is unknown [6].

Associations of GRX4 with chemical compounds

• Grx4 is highly abundant (750-2000 ng/mg of total soluble protein), as determined by a specific enzyme-link immunosorbent assay, and most likely regulated by guanosine 3',5'-tetraphosphate upon entry to stationary phase [1].

Regulatory relationships of GRX4

• Glutaredoxins Grx3 and Grx4 regulate nuclear localisation of Aft1 and the oxidative stress response in Saccharomyces cerevisiae [4].

Other interactions of GRX4

• The mitochondrial forms of Grx3 and Grx4 partially rescue the defects of a grx5 null mutant [7].
• Overexpression of Grx4 attenuates wild type Aft1 activity [3].

References