The primary cilium is a microtubule-based sensory organelle.The molecular mechanism that regulates ciliary dynamics remains elusive.Here,we report an unexpected finding that MLN4924,a small molecule inhibitor of NEDD8-activating enzyme(NAE),blocks primary ciliary formation by inhibiting synthesis/assembly ...
图:NAE激动剂 细胞凋亡抑制剂(cIAP1/2)和X-连锁凋亡抑制剂(XIAP)是两种抗凋亡蛋白(Inhibitor of apoptosis, IAPs),是UPS降解底物,受到Neddylation修饰的调控。激活Neddylation过程,降解抗凋亡蛋白,诱导细胞死亡,理论上也能发挥抗肿瘤作用。研究人员合理设计了化合物VII-31,在MGC803细胞中VII-31能够激活NAE活性,诱导Cu...
本研究发现重要抑癌蛋白PTEN为Neddylation修饰新底物，Neddylation逆转PTEN蛋白的抑癌功能并促进乳腺癌的发生发展，该工作揭示了重要抑癌蛋白PTEN的全新翻译后修饰，丰富了临床上部分肿瘤中PTEN失活的可能机制，拓展了人们对Neddylation功能的认知，为MLN4924应用于临床乳腺癌治疗提供分类治疗和精准治疗的参考依据。 他们发现：...
Abnormal neddylation activation is frequently observed in human cancers and neddylation inhibition has been proposed as a therapy for cancer. Here, we report that MLN4924, a small-molecule inhibitor of neddylation activating enzyme, increases glutamine u
In this study, we used the specific neddylation inhibitor MLN4924 to investigate the effects of neddylation on early murine embryonic development. We also performed transcriptome analysis to uncover the underlying mechanisms. The results showed that inhibition of neddylation led to severe early arrest of...
Inhibiting the protein neddylation pathway using the NEDD8‑activating enzyme inhibitor MLN4924 represents an attractive anticancer strategy having been demonstrated to exhibit promising anticancer efficacy and with tolerable levels of toxicity; however, the mechanism by which MLN4924 inhibits cell proliferatio...
In this work, SENP8 inhibitor candidates were identified in two rounds of virtual high‐throughput screening. Of the ten candidates identified in the first round of screening, four were active in validation experiments to yield an experimental hit rate of 40%. Of the five candidates identified ...
NEDDylationinhibitor molecules, such as MLN4924, which act upon the NEDD8 activating enzyme NAE1, impair HIV-1 infectivity in the presence of A3 G andSAMHD1. This occurs even in the presence of their associated viral accessory proteins,vifandvpx,(Nekorchuk et al., 2013), indicating that NEDD...
Claudia A Vercelli, Corinna A Bauder, Julia S Richter, Francesco Roselli, Anne-Sophie Hafner, Nina Dedic, Carsten T Wotjak, Daniela M Vogt-Weisenhorn, Daniel Choquet, Christoph W Turck, Valentin Stein, Jan M Deussing& Damian Refojo ...
Neddylation inhibitor MLN4924 suppresses growth and migration of human gastric cancer cells MLN4924 is a recently discovered small molecule inhibitor of NEDD8-Activating Enzyme (NAE). Because cullin RING ligase (CRL), the largest family of E3 ubiquitin ligase, requires cullin neddylation for its activi...