Arginyltransferase 1 (ATE1) (ATE1)

Arginyltransferase 1 (ATE1) is a critical enzyme in the N-degron pathway, responsible for the post-translational arginylation of proteins (UniProt: P61923). It transfers an arginine residue from arginyl-tRNA to the N-terminal aspartate, glutamate, or oxidized cysteine of target proteins, marking them for subsequent ubiquitination and proteasomal degradation (PubMed: 22855532). The ATE1 mRNA undergoes extensive alternative splicing to produce multiple isoforms with distinct enzymatic properties and tissue-specific expression patterns (PubMed: 16230347). This process is vital for maintaining protein homeostasis and regulating various cellular processes, including the stress response, cell migration, and cardiovascular development (PubMed: 12446704). In oncology, ATE1 has been shown to act as a context-dependent regulator, where its loss can promote tumor progression and metastasis in certain cancers like prostate and melanoma (PubMed: 25635006). Conversely, its role in stabilizing or destabilizing specific oncoproteins makes it an attractive, albeit complex, therapeutic target. Current research explores the use of small molecule inhibitors like tannic acid and RNA interference (siRNA) to modulate ATE1 activity, though challenges remain regarding its essential role in normal physiology and development (PubMed: 23935036).

Other names

Arginyl-tRNA--protein transferase 1R-transferase 1Arginyltransferase 1ATE1 mRNA

Inhibition of the arginylation of N-terminal aspartate, glutamate, or oxidized cysteine residues, thereby preventing the subsequent ubiquitination and degradation of substrate proteins via the N-degron pathway.