Endothelial cells that line the inner walls of blood vessels are in direct contact with blood and display remarkable heterogeneity in their response to exogenous stimuli. These ECs have unique location-dependent properties determined by the corresponding vascular beds and play an important role in regulating the homeostasis of the vascular system. Evidence suggests that vascular endothelial cells exposed to various environments undergo dynamic phenotypic switching, a key biological program in the context of endothelial heterogeneity, but that might result in EC dysfunction and, in turn, cause a variety of human diseases. Emerging studies show the importance of endothelial to mesenchymal transition (EndMT) in endothelial dysfunction during inflammation. EndMT is a complex biological process in which ECs lose their endothelial characteristics, acquire mesenchymal phenotypes, and express mesenchymal cell markers, such as alpha smooth muscle actin and fibroblast-specific protein 1. EndMT is induced by inflammatory responses, leading to pathological states, including tissue fibrosis, pulmonary arterial hypertension, and atherosclerosis, via dysfunction of the vascular system. Although the mechanisms associated with inflammation-induced EndMT have been identified, unraveling the specific role of this phenotypic switching in vascular dysfunction remains a challenge. Here, we review the current understanding on the interactions between inflammatory processes, EndMT, and endothelial dysfunction, with a focus on the mechanisms that regulate essential signaling pathways. Identification of such mechanisms will guide future research and could provide novel therapeutic targets for the treatment of vascular diseases.

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Previous studies have shown that heat shock factor is constitutively bound to heat shock elements in Saccharomyces cerevisiae. We demonstrate that mutation of the heat shock element closest to the TATA box of the yeast HSP82 promoter abolishes basal-level transcription without markedly affecting inducibility. The mutated heat shock element no longer bound putative heat shock factor, either in vitro or in vivo, but still resided within a nuclease-hypersensitive site in the chromatin. Thus, constitutive binding of heat shock factor to heat shock elements in S. cerevisiae appears to functionally direct basal-level transcription.

Abstract.A 34-KD protein encoded by the SEI-1 gene (p34 ), is a relatively recently discovered oncoprotein that has multiple important biological functions. Our data show that p34 SEI-1 enhances cancer cell survival and promotes tumorigenesis by downregulating the tumor suppressor PTEN, a negative regulator of the PI3K/AKT signaling pathway, and therefore activating the PI3K/AKT signaling pathway. In this process, p34 SEI-1 positively affects NEDD4-1 gene expression both at the transcriptional and protein levels. Furthermore, the expression levels of p34 SEI-1 and NEDD4-1 were found to be coordinated in tumor tissues obtained from patients with breast cancer. We also show that p34 SEI-1 affects the subcellular localization of PTEN.

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