ABSTRACT
The proteasome is the main complex for specific protein degradation in eukaryotic cells, which plays a key role in protein quality control and cell homeostasis maintenance. It is found that abnormal content or function of the proteasome can lead to many human serious diseases such as cancer and neurodegenerative disorders, and several targeted drugs have been developed for the regulation of proteasome activity. Therefore, it is of great academic value and clinical significance to strengthen the research on the precise regulation mechanism of proteasome activity. The content, assembly and activity of the proteasome are regulated rigorously by multiple levels. In this paper, we summarize the composition subunits, structural features, transcriptional regulation and assembly mechanism of proteasome, and focus on the mechanistic regulation and biological significance of post-translational modifications such as phosphorylation, ubiquitination and acetylation on proteasome, which might be helpful to reveal the regulation mechanism of proteasome in the near future.
ABSTRACT
Natural products have played an important role in drug discovery. Today, therapeutics from natural origin count for about 70% of the worldwide human therapeutic sales. For anti-infective treatment even higher figures are reported. This review describes antibacterial and antifungal natural products, semi-synthetic natural products and natural product derived compounds undergoing clinical evaluation or registration from 1998 to end of 2005. In addition, natural product derived drugs launched since 1998 are also discussed in this review.
Subject(s)
Humans , Anti-Bacterial Agents , Chemistry , Pharmacology , Antifungal Agents , Chemistry , Pharmacology , Biological Products , Chemistry , Pharmacology , Drug Resistance, Microbial , Drugs, Investigational , Chemistry , Pharmacology , Echinocandins , Chemistry , Pharmacology , Molecular Structure , Polyenes , Chemistry , PharmacologyABSTRACT
This paper describes natural products, semi-synthetic natural products and natural product-derived compounds used for treating antiparasitic, antiviral and neurological disease that were being evaluated in clinical trials or in registration from 1998 to the end of 2005.