The Anti-Apoptotic Activity of BAG3 Is Restricted by Caspases and the Proteasome

Caspase-mediated cleavage and proteasomal degradation of ubiquitinated proteins are two independent mechanisms for the regulation of protein stability and cellular function. We previously reported BAG3 overexpression protected ubiquitinated clients, such as AKT, from proteasomal degradation and conferred cytoprotection against heat shock. We hypothesized that the BAG3 protein is regulated by proteolysis. caspase-resistant mutant. Caspase and proteasome inhibition resulted in partial and independent protection of BAG3 whereas inhibitors of both blocked BAG3 degradation. STS-induced apoptosis was increased when BAG3 was silenced, and retention of BAG3 was associated with cytoprotection.BAG3 is tightly controlled by selective degradation during STS exposure. Loss of BAG3 under STS injury required sequential caspase cleavage followed by polyubiquitination and proteasomal degradation. The need for dual regulation of BAG3 in apoptosis suggests a key role for BAG3 in cancer cell resistance to apoptosis

Prevalence of otolaryngological disease in a refugee population compared to US‐born patients

ObjectiveLimited data exists regarding otolaryngological (ENT) disease in refugees and we aim to characterize its prevalence.MethodsThis is a retrospective descriptive chart review of adult US-born, immigrant, and refugee patients receiving care at a primary care clinic between 2014 and 2017. We report the prevalence of ENT disease by immigration status. Bivariable and multivariable logistic regression models were conducted to assess differences in prevalence of ENT disease by immigration status.ResultsOf 995 patients included, 202 US-born, 450 immigrants, and 343 were refugees. Immigrants were older (46 years vs. 34 years among refugees, 35.5 years among US-born, p < .001) and more likely to be women (64% vs. 52% among refugees and 56% among US-born, p = .003). Among refugees, 27% were Central American, 22% Chinese, and 9.3% Middle Eastern. Hearing loss and allergic rhinitis were the top two diagnoses among the three groups of immigration status. More refugees had at least 1 ENT diagnosis compared to the other groups (16% vs 14% among immigrants and 6% US-born, p < .001). Refugees were more likely to have at least 1 ENT diagnosis compared to US-born individuals (age and gender adjusted [aOR] 3.40, 95% CI [1.80-6.95], p < .001) and immigrants (aOR 1.62, [1.05-2.51], p = .03).ConclusionENT disease is prevalent among refugees, necessitating standardized evaluation during refugee health assessments and identifying barriers to referral and treatment.Level of evidence2b