RNF14
Description
The RNF14 (ring finger protein 14) is a protein-coding gene located on chromosome 5.
RNF14 is a human gene encoding an enzyme, E3 ubiquitin-protein ligase RNF14, known to be involved in protein-protein interactions due to its RING zinc finger motif. It interacts with the androgen receptor (AR) and acts as a coactivator, inducing AR target gene expression in the prostate. A dominant negative mutant of RNF14 inhibits AR-mediated prostate cancer growth. Additionally, it interacts with class III ubiquitin-conjugating enzymes (E2s) and functions as a ubiquitin-ligase (E3) in ubiquitinating certain nuclear proteins. Five alternatively spliced transcript variants encoding two distinct isoforms have been reported. Notably, RNF14 regulates the relationship between bioenergetic status and inflammation. It influences the expression of mitochondrial and immune-related genes in skeletal muscle, including cytokines and interferon regulatory factors.
E3 ubiquitin-protein ligase RNF14 plays a crucial role in the RNF14-RNF25 translation quality control pathway, which is activated when ribosomes stall during protein synthesis. This pathway promotes the ubiquitination and subsequent degradation of translation factors associated with stalled ribosomes. RNF14 is recruited to stalled ribosomes by the ribosome collision sensor GCN1 and mediates 'Lys-6'-linked ubiquitination of target proteins, leading to their degradation. Specifically, RNF14 ubiquitinates translation factors EEF1A1/eEF1A and ETF1/eRF1 on stalled ribosomes, resulting in their degradation. Additionally, it ubiquitinates ribosomal proteins RPL0, RPL1, RPL12, RPS13, and RPS17. RNF14 is essential for resolving RNA-protein cross-links caused by reactive aldehydes, which trigger translation stress by stalling ribosomes. It catalyzes 'Lys-6'-linked ubiquitination of these cross-links, leading to their removal by the ATP-dependent unfoldase VCP and subsequent degradation by the proteasome. Beyond its role in the response to stalled ribosomes, RNF14 functions as a regulator of transcription in Wnt signaling through its interaction with TCF transcription factors (TCF7/TCF1, TCF7L1/TCF3, and TCF7L2/TCF4). It may also act as a coactivator for androgen- and, to a lesser extent, progesterone-dependent transcription.
RNF14 is also known as ARA54, HFB30, HRIHFB2038, TRIAD2.
