Histone acetyltransferase CBP promotes function of SCF FBXL19 ubiquitin E3 ligase by acetylation and stabilization of its F‐box protein subunit

What is it about?

Total protein content in the cell is regulated by the balance of synthesis and degradation. Ubiquitination is a post-translational modification of protein, which marks protein for degradation. A group of enzyme, called ubiquitin E3 ligases, mediates ubiquitination and degradation of intracellular proteins. We have identified a novel ubiquitin E3 ligase, SCF FBXL19 E3 ligase, which plays a critical role in regulation of inflammatory responses and cytoskeleton dynamics. In this study, we focus on investigating the molecular regulation of FBXL19 protein, which is a key subunit in the ubiquitin E3 ligase. We found that FBXL19 is not a stable protein and its stability is regulated by the ubiquitin-proteasome system, which is one of protein degradation pathway. FBXL19 is not only ubiquitinated, also can be acetylated, which is another post-translational modification. The acetylation of FBXL19 negatively regulates its ubiquitination and degradation. We identified an enzyme, called CBP, targeting FBXL19 for its acetylation. Downregulation or inhibition of CBP reduces FBXL19 acetylation and promotes its degradation. Thus, this study reveals a new molecular mechanism by which CBP regulates ubiquitin E3 ligase through acetylating and stabilizing its subunit. Further, we found that FBXL19 targets Cdc42 for its ubiquitination and degradation. Cdc42 is well known to regulate cell attachment. Our data shows that FBXL19 reduces cell adhesion through degradation of Cdc42.

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