Ubiquitin Fold Modifier 1 (UFM1) and Its Target UFBP1 Protect Pancreatic Beta Cells from ER Stress-Induced Apoptosis

UFM1 is a member of the ubiquitin like protein family. While the enzymatic cascade of UFM1 conjugation has been elucidated in recent years, the biological function remains largely unknown. In this report we demonstrate that the recently identified C20orf116 [1], which we name UFM1-binding protein 1 containing a PCI domain (UFBP1), andCDK5RAP3 interact with UFM1. Components of the UFM1 conjugation pathway (UFM1, UFBP1, UFL1 and CDK5RAP3) are highly expressed in pancreatic islets of Langerhans and some other secretory tissues. Co-localization of UFM1 with UFBP1 in the endoplasmic reticulum (ER)depends on UFBP1. We demonstrate that ER stress, which is common in secretory cells, induces expression of Ufm1, Ufbp1 and Ufl1 in the beta-cell line INS-1E.siRNA-mediated Ufm1 or Ufbp1knockdown enhances apoptosis upon ER stress.Silencing the E3 enzyme UFL1, results in similar outcomes, suggesting that UFM1-UFBP1 conjugation is required to prevent ER stress-induced apoptosis. Together, our data suggest that UFM1-UFBP1participate in preventing ER stress-induced apoptosis in protein secretory cells

The role of cultural heritage in attracting skilled individuals

The purpose of this paper is to examine the role played by built heritages and cultural environments, alongside other locational factors, in explaining the growth of human capital in Sweden. We distinguish between urban, natural and cultural qualities as different sources of regional attractiveness and estimate their influence on the observed growth of individuals with at least three years of higher education during 2001–2010. Neighborhood-level data are used, and unobserved heterogeneity and spatial dependencies are modeled by employing random effects estimations and an instrumental variable approach. Our findings indicate that the local supply of built heritages and cultural environments explain a significant part of human capital growth in Sweden. Results suggest that these types of cultural heritages are important place-based resources with a potential to contribute to improved regional attractiveness and growth