HECT, UBA and WWE domain-containing protein 1 (HUWE1) mRNA (HUWE1)

HUWE1 (HECT, UBA, and WWE domain-containing protein 1) mRNA encodes a massive E3 ubiquitin ligase that serves as a central node in cellular protein homeostasis (UniProt Q7Z6Z7). The protein product, also known as MULE or ARF-BP1, is responsible for the ubiquitination and subsequent proteasomal degradation of critical substrates including the tumor suppressor p53 and the oncogenic transcription factor MYC (PMID: 15958491, PMID: 24210918). In many human cancers, HUWE1 is overexpressed and functions as an oncogene by suppressing p53-mediated apoptosis, thereby promoting tumor growth and survival. Consequently, HUWE1 mRNA is a target for knockdown strategies using siRNA or antisense oligonucleotides to restore tumor suppressor activity. However, HUWE1 also plays an essential role in neural development and DNA repair, with mutations in the gene being a known cause of Turner-type X-linked syndromic intellectual disability (PMID: 24614451). This dual role as both a potential oncogene and an essential developmental factor presents a significant challenge for defining a safe therapeutic window.

Other names

MULEARF-BP1LASU1UREB1HectH9Large structure of UREB1

RNA interference-mediated degradation of HUWE1 mRNA or antisense-mediated inhibition of translation, leading to reduced levels of the HUWE1 E3 ubiquitin ligase protein and subsequent stabilization of its substrates such as p53 (PMID: 15958491).