RNF146
Description
The RNF146 (ring finger protein 146) is a protein-coding gene located on chromosome 6.
RING finger protein 146 is a protein that in humans is encoded by the RNF146 gene.
RNF146 is an E3 ubiquitin-protein ligase that specifically binds poly-ADP-ribosylated (PARsylated) proteins and mediates their ubiquitination and subsequent degradation. It may regulate various cellular processes, including cell survival and DNA damage response. RNF146 acts as an activator of the Wnt signaling pathway by mediating the ubiquitination of PARsylated AXIN1 and AXIN2, two key components of the beta-catenin destruction complex. It interacts with tankyrase proteins (TNKS and TNKS2), which mediate PARsylation of target proteins. RNF146 recognizes and binds tankyrase-dependent PARsylated proteins via its WWE domain, leading to their ubiquitination and degradation. Different ubiquitin linkage types have been observed: TNKS2 undergoes ubiquitination at 'Lys-48' and 'Lys-63', while AXIN1 is only ubiquitinated at 'Lys-48'. RNF146 may regulate TNKS and TNKS2 subcellular location, preventing aggregation at a centrosomal location. It is a neuroprotective protein that protects the brain against N-methyl-D-aspartate (NMDA) receptor-mediated glutamate excitotoxicity and ischemia, by interfering with PAR-induced cell death, called parthanatos. It prevents nuclear translocation of AIFM1 in a PAR-binding dependent manner and does not affect PARP1 activation. RNF146 protects against cell death induced by DNA damaging agents and rescues cells from G1 arrest. It promotes cell survival after gamma-irradiation and facilitates DNA repair.
RNF146 is also known as -.
