Neuralized E3 ubiquitin protein ligase 1 (NEURL1)

Neuralized E3 ubiquitin protein ligase 1 (NEURL1) is a conserved E3 RING-type ligase that regulates the Notch signaling pathway through ubiquitination, primarily promoting the monoubiquitination, endocytosis, and degradation of the Notch ligand Jagged1. It also interacts with and polyubiquitinates substrates such as phosphodiesterase PDE9A, leading to specific protein degradation and modulation of cell signaling. NEURL1 participates in the regulation of cell proliferation, apoptosis, and hippocampal-dependent synaptic plasticity and acts as a physiological tumor suppressor by inhibiting Notch pathway-driven malignant transformation. Its downregulation is linked to neuro-oncological diseases, especially certain brain tumors, where altered NEURL1 expression may contribute to tumor growth and progression. There are currently no drugs specifically known to target NEURL1, and its primary mechanism of therapeutic interest is indirect modulation through upstream regulators or pathway effects.

Other names

NEURL1NEURLNEURL1ARNF67h-neuralized 1neu-1Neuralized-like protein 1ARING finger protein 67RING-type E3 ubiquitin transferase NEURL1NEUR1bA416N2.1

Ubiquitination of substrates (e.g., Jagged1, PDE9A, CPEB3) to regulate their degradation or activity; Downregulation of Notch signaling via Jagged1 ubiquitination; Promotion of protein turnover and modulation of synaptic proteins