RESUMEN
Mutations in the parkin gene encoding an E3 ligase are responsible for autosomal recessive Parkinson's disease. Putative parkin substrates and interacting partners have been identified, but the molecular mechanism underlying parkin-related neurodegeneration is still unclear. We have identified the 20S proteasomal subunit alpha4 (synonyms: PSMA7, XAPC7, subunit alpha type 7) as a new interacting partner of parkin. The C-terminal IBR-RING domain of parkin and the C-terminal part of alpha4 were essential for the interaction. Biochemical studies revealed that alpha4 was not a substrate for parkin-dependent ubiquitylation. Putative functions of the interaction might therefore be substrate presentation to the proteasome or regulation of proteasomal activity. Full-length parkin and parkin lacking the N-terminal ubiquitin-like domain slightly increased the proteasomal activity in HEK 293T cells, in line with the latter hypothesis.
Asunto(s)
Cisteína Endopeptidasas/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Línea Celular , Cisteína Endopeptidasas/química , ADN Complementario/metabolismo , Humanos , Inmunoprecipitación , Modelos Genéticos , Complejos Multienzimáticos/química , Mutación , Células PC12 , Plásmidos/metabolismo , Complejo de la Endopetidasa Proteasomal/química , Complejo de la Endopetidasa Proteasomal/metabolismo , Unión Proteica , Estructura Terciaria de Proteína , Ratas , Transducción de Señal , Técnicas del Sistema de Dos Híbridos , Ubiquitina/química , Ubiquitina-Proteína Ligasas/químicaRESUMEN
Twenty pregnant women who had been given total dose infusion (TDI) of iron dextran at Muhimbili Medical Centre; Dar es Salaam; Tanzania; had their bone marrows examined and red blood cell parameters measured. In 35 per cent of the study group there was no stainable iron in the marrow. The rest showed abnormally increased amounts of marrow iron; and in three of them there was normal in five and increased in the remainder. This increase was probably pregnancy induced
