RESUMO
The ubiquitin-proteasome system (UPS) plays a key role in maintaining cellular protein homeostasis and participates in modulating various cellular functions. Target of rapamycin (TOR), a highly conserved Ser/Thr kinase found across species from yeasts to humans, forms two multi-protein complexes, TORC1 and TORC2, to orchestrate cellular processes crucial for optimal growth, survival, and stress responses. While UPS-mediated regulation of mammalian TOR complexes has been documented, the ubiquitination of yeast TOR complexes remains largely unexplored. Here we report a functional interplay between the UPS and TORC2 in Saccharomyces cerevisiae. Using avo3-2ts, a temperature-sensitive mutant of the essential TORC2 component Avo3 exhibiting TORC2 defects at restrictive temperatures, we obtained evidence for UPS-dependent protein degradation and downregulation of the TORC2 component Avo2. Our results established the involvement of the E3 ubiquitin ligase Ubr1 and its catalytic activity in mediating Avo2 degradation in cells with defective Avo3. Coimmunoprecipitation revealed the interaction between Avo2 and Ubr1, indicating Avo2 as a potential substrate of Ubr1. Furthermore, depleting Ubr1 rescued the growth of avo3-2ts cells at restrictive temperatures, suggesting an essential role of Avo2 in sustaining cell viability under heat stress and/or TORC2 dysfunction. This study uncovers a role of UPS in yeast TORC2 regulation, highlighting the impact of protein degradation control on cellular signaling.
Assuntos
Regulação para Baixo , Alvo Mecanístico do Complexo 2 de Rapamicina , Complexo de Endopeptidases do Proteassoma , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Ubiquitina-Proteína Ligases , Ubiquitina , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Alvo Mecanístico do Complexo 2 de Rapamicina/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , UbiquitinaçãoRESUMO
Primary lymphoma of the cerebellopontine angle (CPA) is rare in the central nervous system. To our knowledge, there have only been 14 cases reported worldwide so far. Here, we report our findings in a 57-year-old man, who presented with bilateral sudden hearing loss followed by left facial palsy within 1 month. Radiologic study and magnetic resonance imaging showed a homogeneous enhancing mass, 1.6 x 0.5 x 1.1cm in size, in the left CPA cistern region with mild extension to the left internal auditory canal. The tumor was removed through left retromastoid craniectomy, and the histopathologic diagnosis of the tumor was confirmed as diffuse large B-cell type malignant lymphoma. After a series of tumor surveys, there was no evidence of other original lymphoma. The patient was treated with chemotherapy (including intra-Ommaya injection with methotrexate and Ara-C and systemic injection with vincristine, methotrexate and ifosfamide) for the primary CPA lymphoma. He was still alive 19 months after the initial treatment.
Assuntos
Neoplasias Cerebelares/complicações , Ângulo Cerebelopontino , Paralisia Facial/etiologia , Perda Auditiva Súbita/etiologia , Linfoma de Células B/complicações , Neoplasias Cerebelares/diagnóstico , Neoplasias Cerebelares/patologia , Humanos , Linfoma de Células B/diagnóstico , Linfoma de Células B/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
The purpose of this study was to investigate knowledge, perceptions of tuberculosis (TB) and intent to receive chest X-ray screening among indigenous (Taiwanese of ethnic Malayo-Polynesian descent) nursing students in Taiwan. A convenience sample was chosen from an technical institute in northern Taiwan that maintained admission quotas and provided scholarships for indigenous students. This school had over 150 classes and around 7,000 students, about 20% -25% of whom were ethnically indigenous. A power analysis based on a pilot study showed that a large effect size required a minimum sample of 485. To attain this number, 50 classes from years one through five were randomly selected based on an expected sampling of 20 students per classroom. In all, 1,000 questionnaires were distributed and 865 returned, for a response rate of 86.5%. A cross-sectional study design was used, and this study was run between the months of February and June 2003. Survey responses were self-reported in two questionnaires that gathered information on respondent knowledge and perceptions regarding TB and intent to take chest X-ray tests. Study results showed a moderate level of general knowledge about TB, misunderstandings regarding transmission vectors, and low perceptions regarding susceptibility. The knowledge score was associated with perceived benefits and barriers to preventing TB. Different places of residence influenced perceived barriers to preventing and treating TB. Age was negatively associated with the perceived benefits of receiving a chest X-ray exam for TB. Indigenous nursing students with higher perceptions of susceptibility and severity and lower perception of barriers on preventing TB had a higher level of intent to take the X-ray exam. Nursing schools must address the subject of TB in-depth and design age-specific curricula that incorporate multifaceted strategies for different students. Additionally, health educators should design health education programs targeted to dispel misconceptions and improve both knowledge and levels of awareness of tuberculosis among the indigenous population in order to enhance their willingness and ability to detect TB.