RESUMO
Ribosome assembly requires precise coordination between the production and assembly of ribosomal components. Mutations in ribosomal proteins that inhibit the assembly process or ribosome function are often associated with ribosomopathies, some of which are linked to defects in proteostasis. In this study, we examine the interplay between several yeast proteostasis enzymes, including deubiquitylases (DUBs) Ubp2 and Ubp14, and E3 ligases Ufd4 and Hul5, and we explore their roles in the regulation of the cellular levels of K29-linked unanchored polyubiquitin (polyUb) chains. Accumulating K29-linked unanchored polyUb chains associate with maturing ribosomes to disrupt their assembly, activate the ribosome assembly stress response (RASTR), and lead to the sequestration of ribosomal proteins at the intranuclear quality control compartment (INQ). These findings reveal the physiological relevance of INQ and provide insights into mechanisms of cellular toxicity associated with ribosomopathies.
Assuntos
Poliubiquitina , Proteínas Ribossômicas , Ribossomos , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Proteínas Ribossômicas/metabolismo , Proteínas Ribossômicas/genética , Ribossomos/metabolismo , Ribossomos/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Poliubiquitina/metabolismo , Poliubiquitina/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Proteostase , Núcleo Celular/metabolismoRESUMO
Este folleto examina cinco preguntas fundamentales sobre la esquizofrenia: Que es? Cual es su causa? Como se trata? Pueden otras personas ayudar? Cuales son los tratamientos? Disponer de informacion correcta puede ayudar a eliminar las ideas erroneas y, por lo tanto, a disminuir el temor, la verguenza y la desesperanza asociadas frecuentemente con esta enfermedad.