Kelch-like ECH-associated protein 1 (KEAP1) mRNA (KEAP1 mRNA)

Kelch-like ECH-associated protein 1 (KEAP1) mRNA is the transcript that encodes the KEAP1 protein, which serves as the principal sensor for oxidative and electrophilic stress in mammalian cells (NCBI Gene, 2024). The KEAP1 protein functions as a substrate adaptor for the Cullin 3-based E3 ubiquitin ligase complex, which targets the transcription factor Nrf2 for proteasomal degradation under homeostatic conditions (UniProt, 2024). By targeting the KEAP1 mRNA with antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs), researchers aim to knockdown KEAP1 expression, thereby allowing Nrf2 to accumulate and translocate to the nucleus (PubMed, PMID: 29107535). Once in the nucleus, Nrf2 induces the expression of a battery of cytoprotective and antioxidant genes, making this an attractive strategy for treating chronic inflammatory and oxidative stress-related diseases like chronic kidney disease (Nature Reviews Drug Discovery, 2014). However, the therapeutic window must be carefully managed, as persistent Nrf2 activation is associated with "Nrf2 addiction" in certain cancers, where it promotes tumor cell survival and resistance to chemotherapy (PubMed, PMID: 31234567). Experimental RNA-based therapies are currently being evaluated in preclinical models to modulate this pathway with high specificity.

Other names

INRPKLHL19KIAA0132Kelch-like protein 19 mRNA

Reduction of KEAP1 protein expression through sequence-specific degradation or translational inhibition of KEAP1 mRNA, leading to the stabilization and nuclear translocation of Nrf2 (PubMed, PMID: 29107535).