High impact information on DBP5

• This aberrant accumulation of Mex67p with RNA and the cold-sensitive growth phenotype of a dbp5 allele are suppressed by a mex67 mutation [1].
• In contrast, the dbp5-trapped mRNPs lack Yra1p [1].
• These findings suggest that the Nup159 NTD functions in mRNA export as a binding platform, tethering shuttling Dbp5 molecules at the nuclear periphery and locally concentrating this mRNA remodeling factor at the cytoplasmic face of the NPC [2].
• Residue substitutions in a conserved loop of the NTD abolish in vitro binding to Dbp5, a DEAD box helicase required for mRNA export [2].
• Dominant mutations in DBP5 and GLE1 that rescue mRNA export phenotypes associated with the lack of InsP6 mimic the InsP6 effects in vitro [3].

Biological context of DBP5

• Analysis of protein databases suggests most eukaryotic genomes encode a DEAD-box protein that is probably a homolog of yeast Dbp5p/Rat8p [4].
• These results suggest that changes in the localization of Rat8p contribute to the selective export of mRNA in ethanol stressed cells, and also indicate differences in mRNA export between the heat shock response and ethanol stress response [5].

Anatomical context of DBP5

• Deletion of this portion of Rat7p (Rat7pDeltaN) results in strong defects in mRNA export and eliminates association of Dbp5p with nuclear pores [6].
• Surprisingly, Dbp5p is present predominantly, if not exclusively, in the cytoplasm, and is highly enriched around the nuclear envelope [7].
• The functions of Dbp5p are likely to be conserved, since its potential homologues can be found in a variety of eukaryotic cells [7].

Associations of DBP5 with chemical compounds

• Exposure to 10% ethanol led to dissociation of Rat8p from NPCs in both wild-type and rip1Delta cells [8].
• Interestingly, Gle1 binds directly to inositol hexakisphosphate (InsP6) and InsP6 potentiates the Gle1-mediated stimulation of Dbp5 [3].

Physical interactions of DBP5

• Dbp5p interacts with Gle1p independently of the N-terminus of Dbp5p [6].
• Moreover, Mex67 bound mRNA accumulates at the nuclear rim in a temperature-sensitive dbp5 mutant when the nuclear exosome is impaired [1].
• In vitro binding experiments revealed that Gfd1p and Dbp5p bind directly to the C-terminal part of Zds1p [9].

Regulatory relationships of DBP5

• Overexpression of Dbp5p completely suppressed the growth and mRNA export defects of rat7DeltaN cells and resulted in weaker suppression in cells carrying rat7-1 or the rss1-37 allele of GLE1 [6].
• Overexpression of DBP5 specifically suppressed mRNA export and growth defects of an ipk1 nup42 mutant defective in InsP6 production and Gle1 localization [10].

Other interactions of DBP5

• In a screen for high-copy suppressors of the rat8-2 allele of DBP5, we identified YMR255w, now called GFD1 [6].
• The DEAD-box protein Dbp5p is required to dissociate Mex67p from exported mRNPs at the nuclear rim [1].
• By using the two-hybrid system, we showed that Zds1p interacts in vivo with both Gfd1p and Dbp5p [9].
• We also found that the nuclear accumulation of Rat8p is caused by a defect in the Xpo1p/Crm1p exportin [5].
• In addition, deletion of dhh1, when placed in conjunction with the mutant dbp5 and ded1 alleles, resulted in a synergistically lethal effect, suggesting that Dhh1p may have a role in mRNA export and translation [11].

Analytical, diagnostic and therapeutic context of DBP5

• By immunoelectron microscopy, the nuclear envelope-bound fraction of Dbp5 has been localized to the cytoplasmic fibrils of the nuclear pore complex (NPC) [12].

References