RESUMO
A secretory defect causes specific and significant transcriptional repression of both ribosomal protein and rRNA genes (K. Mizuta and J. R. Warner, Mol. Cell. Biol. 14:2493-2502, 1994), suggesting the coupling of plasma membrane and ribosome syntheses. In order to elucidate the molecular mechanism of the signaling pathway, we isolated a cold-sensitive mutant with a mutation in a gene termed RRS1 (regulator of ribosome synthesis), which appeared to be defective in the signaling pathway. The rrs1-1 mutation greatly reduced transcriptional repression of both rRNA and ribosomal protein genes that is caused by a secretory defect. RRS1 is a novel, essential gene encoding a nuclear protein of 203 amino acid residues that is conserved in eukaryotes. A conditional rrs1-null mutant was constructed by placing RRS1 under the control of the GAL1 promoter. Rrs1p depletion caused defects in processing of pre-rRNA and assembly of ribosomal subunits.
Assuntos
Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Proteínas Nucleares/genética , Ribossomos/genética , Ribossomos/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Sequência de Aminoácidos , Proteínas Fúngicas/metabolismo , Genes Fúngicos , Dados de Sequência Molecular , Proteínas Nucleares/metabolismo , Alinhamento de SequênciaRESUMO
Endometriosis, a disease affecting 3-10% of women of reproductive age, is characterized by the ectopic growth of endometrial tissue. Increasingly, endometriosis is also becoming recognized as a condition in which ectopic endometrial cells exhibit abnormal proliferative and apoptotic regulation in response to appropriate stimuli. Apoptosis plays a critical role in maintaining tissue homeostasis and represents a normal function to eliminate excess or dysfunctional cells. Accumulated evidence suggests that, in healthy women, endometrial cells expelled during menstruation do not survive in ectopic locations because of programmed cell death, while decreased apoptosis may lead to the ectopic survival and implantation of these cells, resulting in the development of endometriosis. Both the inability of endometrial cells to transmit a 'death' signal and the ability of endometrial cells to avoid cell death have been associated with increased expression of anti-apoptotic factors and decreased expression of pre-apoptotic factors. This paper is a review of the recent literature focused on the differential expression of apoptosis-associated molecules in the normal endometria of women without endometriosis, and in the eutopic and ectopic endometria of women with endometriosis. The role of apoptosis in the pathogenesis of endometriosis and the basic and clinical research on the current medical treatment for endometriosis from the view of apoptosis will be discussed.
Assuntos
Apoptose , Resistência a Medicamentos/genética , Endometriose/etiologia , Endometriose/patologia , Endométrio/citologia , Apoptose/genética , Apoptose/fisiologia , Inibidores da Aromatase/uso terapêutico , Danazol/uso terapêutico , Endometriose/tratamento farmacológico , Endométrio/efeitos dos fármacos , Antagonistas de Estrogênios/uso terapêutico , Feminino , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Progesterona/uso terapêuticoRESUMO
BACKGROUND: A defect in the secretory pathway causes the transcriptional repression of both rRNA and ribosomal protein genes in Saccharomyces cerevisiae, suggesting a coupling of ribosome synthesis and plasma membrane synthesis. Rrs1p, an essential nuclear protein, is required for the secretory response. RESULTS: EBP2, encoding the yeast homologue of a human protein that interacts with Epstein-Barr virus Nuclear Antigen 1, was cloned in a two-hybrid screen using RRS1 as a bait. The rrs1-1 mutation, which produces Rrs1p without the C-terminal half and causes a defect in the secretory response, almost abolished the interaction with Ebp2p. Ebp2p is essential for growth and is mainly localized in the nucleolus. The effects of Ebp2p depletion on ribosome biogenesis is quite similar to that of Rrs1p depletion; in the Ebp2p-depleted cells, the rate of pre-rRNA processing is slower, and significantly less mature 25S rRNA is produced compared to those in wild-type cells. The polysome pattern indicates that Ebp2p-depletion causes a decrease of 80S monosomes and polysomes, an accumulation of 40S subunits, and the appearance of half-mer polysomes. CONCLUSIONS: Ebp2p is required for the maturation of 25S rRNA and 60S subunit assembly. Ebp2p may be one of the target proteins of Rrs1p for executing the signal to regulate ribosome biogenesis.