ABSTRACT
Proteolysis-targeting chimeras (PROTACs) are small-molecule protein degraders based on the ubiquitin-proteasome system. Recently, the development of specific small-molecule ligands for several E3 ligases (CRL4CRBN, CRL2VHL and cIAP) have significantly advanced the PROTACs technology. Several PROTACs against various oncogenic proteins including bromodomain-containing protein 4 (BRD4), estrogen receptor (ER) and androgen receptor (AR) have been developed and considered a novel approach for therapy of cancers. There are advantages of the new technology over the traditional small-molecule strategies. This review article provides a summary on the recent progress in the small-molecule-based PROTACs as antitumor drugs, and the challenges of this technology.
ABSTRACT
The regulation of proline accumulation in seedlings of rice (Oryza sativa L. cv. Badami) was investigated. The increasing concentration of NaCl from 0.5 to 2.5 % progressively increased the proline content in rice. Proline accumulation caused by NaCl was related to protein proteolysis, an increase in OAT, P5CS, P5CR activity, a decrease in PDH activity. The maximum increase in proline content was recorded at 2.5 % NaCl concentration as compared to control and other concentrations of NaCl. The highest significant activity of proline synthesizing enzymes, D1-Pyrrolline-5-carboxylate synthetase, D1-Pyrrolline-5-carboxylate reductase and Ornithine-d-aminotransferase with a lowest activity of proline hydrolysis enzymes; Proline dehydrogenase were also recorded at 2.5 % salinity over control and other concentrations of NaCl with a in-significant increase in the activity of D1-Pyrrolline-5-carboxylate synthetase and Ornithine-d-aminotransferase at 0.5 % concentration of NaCl over control. Externally the addition of 300mg MnCl2, 220 ml-1 ½ strength Hoagland solution, having 1% NaCl, was seen to increase a 893.9 % in proline content of this variety as compared to control.