The E3 ubiquitin ligase SCF(Fbxo7) mediates proteasomal degradation of UXT isoform 2 (UXT-V2) to inhibit the NF-?B signaling pathway

Ubiquitously eXpressed Transcript isoform 2 (UXTV2) is a prefoldin-like protein involved in NF-?B signaling, apoptosis, and the androgen estrogen response. UXT-V2 cofactor transcriptional enhanceosome, its knockdown inhibits TNF-? -induced activation. Fbxo7 an F-box that interacts with SKP1, Cullin1 RBX1 proteins to form SCF(Fbxo7) E3 ubiquitin ligase complex. negatively regulates signaling through TRAF2 cIAP1 ubiquitination. We combine co-immunoprecipitation, ubiquitination vitro vivo, cycloheximide chase assay, chain restriction analysis microscopy investigate interaction between overexpressed UXT-V2-HA. The Ubl domain of contributes UXTV2. This substrate polyubiquitinated by K48 K63 linkages vivo. post-translational modification decreases stability promotes proteasomal degradation. further show UXTV1, alternatively spliced UXT, containing 12 additional amino acids at N-terminus as compared UXTV2, also ubiquitinated Fbxo7. Moreover, FBXO7 accumulation, overexpression Fbxo7-?F-box protects from degradation enhances responsiveness reporter. find colocalizes cell nucleus. Together, our study reveals mediates causing inhibition pathway. Discovering new substrates ubiquitin-ligase understand function different diseases such cancer Parkinson.