Disease relevance of Dnaja3

• Mice deficient in Dnaja3 developed dilated cardiomyopathy (DCM) and died before 10 weeks of age [1].
• Here we report that the mitochondrial chaperone Hsp40, also known as Dnaja3 or Tid1, is differentially expressed during cardiac development and pathological hypertrophy [1].
• We show that GSE-Tid1 enhances immortalization by human papillomavirus E7 and simian virus 40 T antigen and cooperates with activated ras for transformation [2].

High impact information on Dnaja3

• Progressive respiratory chain deficiency and decreased copy number of mitochondrial DNA were evident in cardiomyocytes lacking Dnaja3 [1].
• 5. To assess the function of Tid1 in embryonic cells, mouse embryonic fibroblasts with the homologous Tid1 floxed allele were produced [3].
• Tid1, a cochaperone of the heat shock 70 protein and the mammalian counterpart of the Drosophila tumor suppressor l(2)tid, is critical for early embryonic development and cell survival [3].
• Nonetheless, Tid1-deficient blastocysts were viable, hatched, formed an inner cell mass and trophectoderm, and implanted (E4.5), suggesting that the homozygous mutant embryos die between E4.5 and E7 [3].
• Tid1 removal in these cells led to massive cell death [3].

Biological context of Dnaja3

• We therefore propose that Tid1 contributes to senescence by acting as a repressor of NF-kappaB signaling [2].
• Expression of Tid1 is upregulated upon cellular senescence in rat and mouse embryo fibroblasts and premature senescence of REF52 cells triggered by activated ras [2].

Anatomical context of Dnaja3

• In immunofluorescence experiments, GAP and Tid-1 were shown to colocalize at perinuclear mitochondrial membranes in response to epidermal growth factor stimulation [4].

References