Regulation of Stress-Inducible Phosphoprotein 1 Nuclear Retention by Protein Inhibitor of Activated STAT PIAS1

Stress-inducible phosphoprotein 1 (STI1), a cochaperone for Hsp90, has been shown to regulate multiple pathways in astrocytes, but its contributions to cellular stress responses are not fully understood. We show that in response to irradiation-mediated DNA damage stress STI1 accumulates in the nucleus of astrocytes. Also, STI1 haploinsufficiency decreases astrocyte survival after irradiation. Using yeast two-hybrid screenings we identified several nuclear proteins as STI1 interactors. Overexpression of one of these interactors, PIAS1, seems to be specifically involved in STI1 nuclear retention and in directing STI1 and Hsp90 to specific sub-nuclear regions. PIAS1 and STI1 co-immunoprecipitate and PIAS1 can function as an E3 SUMO ligase for STI. Using mass spectrometry we identified five SUMOylation sites in STI1. A STI1 mutant lacking these five sites is not SUMOylated, but still accumulates in the nucleus in response to increased expression of PIAS1, suggesting the possibility that a direct interaction with PIAS1 could be responsible for STI1 nuclear retention. To test this possibility, we mapped the interaction sites between PIAS1 and STI1 using yeast-two hybrid assays and surface plasmon resonance and found that a large domain in the N-terminal region of STI1 interacts with high affinity with amino acids 450-480 of PIAS1. Knockdown of PIAS1 in astrocytes impairs the accumulation of nuclear STI1 in response to irradiation. Moreover, a PIAS1 mutant lacking the STI1 binding site is unable to increase STI1 nuclear retention. Interestingly, in human glioblastoma multiforme PIAS1 expression is increased and we found a significant correlation between increased PIAS1 expression and STI1 nuclear localization. These experiments provide evidence that direct interaction between STI1 and PIAS1 is involved in the accumulation of nuclear STI1. This retention mechanism could facilitate nuclear chaperone activity. Molecular & Cellular Proteomics 12: 10.1074/mcp.M113.031005, 3253-3270, 2013

Diagnóstico citopatológico de tumores neuroepiteliais pela técnica do esfregaço

Estudamos grupo de 198 casos de tumores neuroepiteliais com diagnóstico peroperatório feito pela análise citológica de esfregaços, comparando seus índices de acuidade com o diagnóstico final em cortes de parafina. Em 90,6% dos casos, o diagnóstico final obtido na parafina foi similar ao feito em esfregaços. No grupo de casos em que o diagnóstico citológico não foi confirmado pelos cortes em parafina, na maioria dos casos não foi afetada a conduta neurocirúrgica imediata, representando diferenças em graduação de astrocitomas e gliomas mistos. Os critérios citológicos nos principais grupos de tumores são apresentados, junto com as dificuldades para a interpretação deste método valioso para diagnóstico per-operatório

Von hippel-lindaus disease: Report of three cases and review of the literature Doença de von Hippel-Lindau: relato de três casos e revisão da literatura

The authors present the autopsy findings of two related patients and the biopsy findings of a thrid member of the family. The oldest member was 34 years old at death and on postmortem examination he had haemangioblastomas in the retina, cerebellum, medulla and spinal cord. Other findings were renal cell carcinoma, phaechromocytoma, cysts of kidney and pancreas, hydromyelia and atypical meningiomas. His brother died when 30 years old. The autopsy revealed haemangioblastomas of cerebellum, renal cell carcinoma and a clear cell cystadenoma of epididymus. The third patient was the daughter of the first and presented with headache and dizziness. CT-scan showed a cerebellar haemangioblastoma. Epidemiological considerations on the commonest visceral and CNS lesions and a review of current diagnostic criteria are discussed.Os autores relatam os achados de autópsia de dois pacientes de uma mesma família e o diagnóstico por biópsia de hemangioblastoma de um terceiro membro desta mesma família. O primeiro paciente tinha 34 anos por ocasião do óbito e os achados de necrópsia mostraram hemangioblastoma de retina, cerebelo, bulbo e medula espinhal, além de carcinoma renal, feocromocitoma, lesões císticas de rim e pâncreas, hidromielia e meningiomas atípicos. Seu irmão morreu com 30 anos de idade e a autópsia revelou hemangioblastomas de cerebelo, carcinoma renal e cistoadenoma de células claras de epididimo. A terceira paciente era filha do primeiro paciente e apresentou cefaléia e ataxia. A tomografia computadorizada mostrou lesão cerebelar cística e a biópsia confirmou tratar-se de hemangioblastoma. São feitas considerações epidemiológicas sobre lesões viscerais e do sistema nervoso mais comumente encontradas, além de discutir critérios diagnósticos

Abscesso actinomicótico do cerebelo: relato de caso Actinomycotic abscess of the cerebellum: case report

Acometimento do sistema nervoso central por actinomicetos é extremamente raro. Os autores descrevem um caso de actinomicose de cerebelo, com diagnóstico estabelecido após remoção cirúrgica da lesão e tratamento com sucesso com penicilina endovenosa e oral. Breve revisão da literatura sobre o envolvimento do sistema nervoso na actinomicose é apresentada.A 38 year-old man presented fever and a clinical picture of intracranial hypertension and ataxic syndrome. A CT-scan disclosed an expanding lesion of the cerebellum. Surgical excision of the lesion was performed and pathological examination made the diagnosis of an actinomycotic abscess. The probable primary source of infection were the lungs and/or oral cavity. The postoperative course was uneventful, with complete recovery after a long period of treatment with penicillin (IV and PO). The authors review some aspects about central nervous system involvement in actinomycosis