James E. Brownell

TL;DR: MLN4924 disrupts cullin-RING ligase-mediated protein turnover leading to apoptotic death in human tumour cells by a new mechanism of action, the deregulation of S-phase DNA synthesis, suggesting that NAE inhibitors may hold promise for the treatment of cancer.

TL;DR: Recent advances in understanding the role of some of these enzymes are highlighted and how these new insights may be the key to developing novel therapeutics for diseases including immuno-inflammatory disorders, cancer, infectious diseases, cardiovascular disease and neurodegenerative disorders.

TL;DR: Insight is revealed into the mechanism of E1s and a general strategy for selective inhibition of UBL conjugation pathways is suggested and compounds resembling MLN4924 demonstrate the ability to form analogous adducts with other ubiquitin-like proteins catalyzed by their cognate-activating enzymes.

TL;DR: It is shown that overexpression of topors results in a proteasome-dependent decrease in p53 protein expression in a human osteosarcoma cell line and suggests that topors functions as a ubiquitin ligase for multiple transcription factors.

TL;DR: In cell and xenograft models of cancer, it is identified treatment-emergent heterozygous mutations in the adenosine triphosphate binding pocket and NEDD8-binding cleft of NAEβ as the primary mechanism of resistance to MLN4924.