SCFFBXO28-mediated self-ubiquitination of FBXO28 promotes its degradation.

SCFFBXO28-mediated self-ubiquitination of FBXO28 promotes its degradation.
Cell Signal. 2019 Oct 30;:109440
Authors: Cai L, Liu L, Li L, Jia L
Abstract
The F-box protein is the substrate recognition subunit of SCF (SKP1/CUL1/F-box) E3 ubiquitin ligase complex, a multicomponent RING-type E3 ligase involved in the regulation of numerous cellular processes by targeting critical regulatory proteins for ubiquitination. However, whether and how F-box proteins are regulated is largely unknown. Here we report that FBXO28, a poorly characterized F-box protein, is a novel substrate of SCF E3 ligase. Pharmaceutical or genetic inhibition of neddylation pathway that is required for the activation of SCF stabilizes FBXO28 and prolongs its half-life. Meanwhile, FBXO28 is subjected to ubiquitination and cullin1-based SCF complex promotes FBXO28 degradation. Moreover, deletion of F-box domain stabilizes FBXO28 and knockdown of endogenous FBXO28 strongly upregulates exogenous FBXO28 expression. Taken together, these data reveal that SCFFBXO28 is the E3 ligase responsible for the self-ubiquitination and proteasomal degradation of FBXO28, providing a new clue for the upstream signaling regulation for F-box proteins.
PMID: 31678254 [PubMed - as supplied by publisher]

Source: Cellular Signalling - October 29, 2019 Category: Cytology Authors: Cai L, Liu L, Li L, Jia L Tags: Cell Signal Source Type: research