ABSTRACT
Polo-box domain 1 (PBD1) is a characteristic domain of polo-like kinase 1 (PLK1), which locates in C-terminal and can influence the catalytic activity and specific subcellular locations of PLK1. At present, most PLK1 inhibitors are developed to occupy the ATP pocket or its close sites. However, this kind of PLK1 inhibitors is difficult to pursue target selectivity and may encounter cross drug resistance with other kinase inhibitors due to the conserved sequence of ATP pocket. Recently, PBD1, with aberrant specificity in sequence and structure, has attracted enormous interests as the alternative target to the discovery of corresponding inhibitors for anti-tumor drugs. The structure and function of PBD1 as well as the advances of its inhibitors are reviewed in this paper.
Subject(s)
Humans , Benzocycloheptenes , Chemistry , Pharmacology , Benzoquinones , Chemistry , Pharmacology , Cell Cycle Proteins , Chemistry , Cell Line, Tumor , Cell Proliferation , Indole Alkaloids , Chemistry , Pharmacology , Lactams , Chemistry , Pharmacology , Peptides, Cyclic , Chemistry , Pharmacology , Phosphopeptides , Chemistry , Pharmacology , Protein Serine-Threonine Kinases , Chemistry , Proto-Oncogene Proteins , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To explore the process of refuse decomposition in hybrid bioreactor landfill.</p><p><b>METHODS</b>The bioreactor landfill was operated in sequencing of facultative-anaerobic and aerobic conditions with leachate recirculation, pH, COD, and ammonia in the leachate and pH, biodegradable organic matter (BDM), and cation exchange capacity (CEC) in refuse were detected.</p><p><b>RESULTS</b>CEC increased gradually with the degradation of refuse, which was negatively correlated with BDM. COD and ammonia in the leachate was declined to 399.2 mg L(-1) and 20.6 mg N L(-1), respectively, during the 357-day operation. The respective concentrations of ammonia and COD were below the second and the third levels of current discharge standards in China.</p><p><b>CONCLUSION</b>The refuse is relatively stable at the end of hybrid bioreactor landfill operation. Most of the readily biodegradable organic matter is mineralized in the initial phase of refuse degradation, whereas the hard-biodegradable organic matter is mainly humidified in the maturity phase of refuse degradation.</p>