RESUMO
Ded1 is a fission yeast DEAD box protein involved in translation. We isolated Ded1 in a screen for multi-copy suppressors of a cold-sensitive, loss-of-function mutant of the cyclin-dependent kinase Cdc2. The checkpoint protein kinase Chk1, required for cell cycle arrest in response to DNA damage, was also isolated in this screen. Ded1 interacts with Chk1 in a two-hybrid screen, and this physical interaction can be recapitulated in Schizosaccharomyces pombe. The Ded1 polypeptide is modified in response to heat shock and depletion of carbon source. These two stressors appear to cause different modifications. Thus, the Ded1 protein appears to respond to particular types of cellular stress and may influence the activity of Cdc2 as a result.
Assuntos
Proteína Quinase CDC2/metabolismo , Proteínas de Ciclo Celular , Proteínas Fúngicas/metabolismo , Proteínas Quinases/metabolismo , RNA Helicases , Proteínas de Schizosaccharomyces pombe , Proteína Quinase CDC2/química , Ciclo Celular , Quinase 1 do Ponto de Checagem , RNA Helicases DEAD-box , Dano ao DNA , Proteínas Fúngicas/química , Temperatura Alta , Immunoblotting , Sistema de Sinalização das MAP Quinases , Modelos Biológicos , Mutação , Fenótipo , Ligação Proteica , Biossíntese de Proteínas , Proteínas Quinases/química , Estrutura Terciária de Proteína , Schizosaccharomyces/metabolismo , Transdução de Sinais , Temperatura , Fatores de Tempo , Técnicas do Sistema de Duplo-Híbrido , Regulação para CimaRESUMO
Although the molecular mechanism of aging is unknown, a progressive increase with age in the concentration of damaged macromolecules, especially proteins, is likely to play a central role in senescent decline. In this paper, we discuss evidence that the progressive decrease in protein synthesis and turnover can be the primary cause of the increase in the concentration of damaged proteins with age. Conversely, protein damage itself is likely to be the cause of the decrease in protein turnover. This could establish a positive feedback loop where the increase in protein damage decreases the protein turnover rate, leading to a further increase in the concentration of damaged proteins. The establishment of such a feedback loop should result in an exponential increase in the amount of protein damage-a protein damage catastrophe-that could be the basis of the general deterioration observed in senescent organisms.