LYL1 Degradation by the Proteasome Is Directed by a N-Terminal PEST Rich Site in a Phosphorylation-Independent Manner

Background: The Lymphoblastic leukemia 1 (LYL1) gene is a proto-oncogenic transcription factor found upregulated in patients with T-cell acute lymphoblastic leukemia (T-cell ALL). Initially, the upregulation was described to be as a result of a translocation. However, further studies revealed that transcriptional upregulation of LYL1could also occur without translocations. In addition, post-translational mechanisms, such as protein degradation could influence LYL1 expression as well. Methodology/Principal Findings: In this study, we considered possible post-translational regulation of Lyl1, and investigated fundamental mechanisms governing LYL1 degradation in cell-based culture assays. We identify a PEST sequence motif located in the N-terminus of LYL1, which determines the efficiency of LYL1 degradation by the proteasome. The absence of the PEST degradation site leads to accumulation or upregulation of LYL1. We also show that LYL1 is phosphorylated by MAPK at S36, and determined that proteasomal degradation of LYL1 occurs in a phosphorylationindependent manner. Conclusions/Significance: Understanding LYL1 degradation is a step forward not only towards deciphering the normal function and regulation of LYL1, but could suggest post-translational mechanisms for upregulation of LYL1 that ma

Assessing storm surge risk under future sea-level rise scenarios: a case study in the North Adriatic coast

Low-lying coastal areas are often prone to storm surge flooding that can render severe damages to properties, destruction of habitats, threat to human safety and the environment. The impacts of coastal flooding are also expected to increase in the future as a consequence of global climate change and sea-level rise. This paper presents a comprehensive assessment of the potential risks raised by storm surge and sea-level rise on multiple coastal targets (i.e., population, buildings, infrastructures, agriculture, natural and semi-natural environments and cultural heritage) in the Northern Adriatic coast in Italy. Through the assessment of hazard, exposure, vulnerability and risk, a Regional Risk Assessment (RRA) methodology allowed identifying and prioritizing hot-spot risk areas and targets requiring particular attention for the definition of adaptation strategies. Hazard scenarios were based on the analysis of tide gauge data (elaborated with the Joint Probability Method) and of different sea-level rise projections for the year 2100. Geographical-information analysis was then used to characterize vulnerability patterns of exposed natural and human systems and to make a spatial ranking of risks. Maps produced for the worst scenario showed that beaches are the target at higher risk (with more than 90% of the surface in the higher relative risk class) due to the low elevation and high proximity to the coastline. Also cultural heritage (i.e., villas, historical buildings and roads) and wetlands are highly threatened by storm surge flooding. The relative risks will be lower (i.e., between 25% and 40% of their surface/length in the higher relative risk class) for most of the other receptors (i.e., local roads, railways, natural and semi-natural environments and agricultural areas), including population and buildings that are mostly classified in lower risk classes. The overall results of the assessment, including maps and risk metrics, can be useful to rise the attention of coastal managers about the need to adapt to climate change, developing climate-proof policies and programs for the sustainable management of coastal zones