Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our recent study found that 30% of young genes were essential for viability that determines development through stages from embryo to pupae in Drosophila melanogaster, revealing rapidly evolving genetic components involved in the evolution of development. Meanwhile, many young genes did not produce complete lethal phenotype upon constitutive knockdown, suggesting that they may not be essential for viability. These genes, nevertheless, were fixed by natural selection, and might play an important functional role in their adult stage. Here we present a detailed demonstration that a newly duplicated serine-type endopeptidase gene that originated in the common ancestor in the D. melanogaster subgroup 6~11 million years ago, named Slfc, revealing a strong effect in post-eclosion. Although animals survived constitutive knockdown of Slfc to adult stage, however, their life span reduced significantly by two-thirds compared to wildtype. Furthermore, the Slfc-RNAi males dropped their fertility to less than 10% of the wildtype level, with over 80% of these males being sterile. The Slfc-RNAi females, on the other hand, showed a slight reduction in fertility. This case study demonstrates that a young gene can contribute to fitness on the three important traits of life history in adults, including the life expectancy, male fertility and female fertility, suggesting that new genes can quickly evolve and impact multiple phenotypes.
Fly (Austin)
PMID:Roles of young serine-endopeptidase genes in survival and reproduction revealed rapid evolution of phenotypic effects at adult stages. 2194 55

The TOR signaling pathway is crucial in the translation of nutritional inputs into the protein synthesis machinery regulation, allowing animal growth. We recently identified the Bud32 (yeast)/PRPK (human) ortholog in Drosophila, Prpk (p53-related protein kinase), and found that it is required for TOR kinase activity. Bud32/PRPK is an ancient and atypical kinase conserved in evolution from Archeae to humans, being essential for Archeae. It has been linked with p53 stabilization in human cell culture and its absence in yeast causes a slow-growth phenotype. This protein has been associated to KEOPS (kinase, putative endopeptidase and other proteins of small size) complex together with Kae1p (ATPase), Cgi-121 and Pcc1p. This complex has been implicated in telomere maintenance, transcriptional regulation, bud site selection and chemical modification of tRNAs (tRNAs). Bud32p and Kae1p have been related with N6-threonylcarbamoyladenosine (t (6)A) synthesis, a particular chemical modification that occurs at position 37 of tRNAs that pair A-starting codons, required for proper translation in most species. Lack of this modification causes mistranslations and open reading frame shifts in yeast. The core constituents of the KEOPS complex are present in Drosophila, but their physical interaction has not been reported yet. Here, we present a review of the findings regarding the function of this complex in different organisms and new evidence that extends our recent observations of Prpk function in animal growth showing that depletion of Kae1 or Prpk, in accordance with their role in translation in yeast, is able to induce the unfolded protein response (UPR) in Drosophila. We suggest that EKC/KEOPS complex could be integrating t (6)A-modified tRNA availability with translational rates, which are ultimately reflected in animal growth.
Fly (Austin)
PMID:The Drosophila EKC/KEOPS complex: roles in protein synthesis homeostasis and animal growth. 2344 56