Members of the tripartite motif (TRIM) protein family, including the E3 ubiquitin ligase TRIM32, have been implicated in a wide range of cellular processes, but how signalling pathways act to regulate these proteins is largely unknown. Previous studies have shown that phosphorylation by protein kinase A (PKA) negatively regulates a particular E3 ubiquitin ligase by recruiting the protein 14-3-3. On page 2014, Tohru Ichimura, Naomi Hachiya and colleagues now show that the 14-3-3 proteins have a wider repertoire in their regulation of E3 ubiquitin ligases. Using a quantitative proteomics screen of 14-3-3 interactions in PKA signalling in a cell line, the authors show that most of these interactions are located downstream of PKA. The screen identified TRIM32, together with six other E3 ubiquitin ligases, which was confirmed to be a 14-3-3-binding partner, with 14-3-3 binding TRIM32 directly when the ligase is phosphorylated by PKA at Ser651. The 14-3-3–TRIM32 interaction was then shown to prevent autoubiquitylation and the formation of TRIM32-containing cytoplasmic bodies – potential autoregulatory mechanisms that control the concentration of soluble free TRIM32. Furthermore, the negative regulation by 14-3-3 is partly a consequence of blocking TRIM32 higher-order self-association but not homodimerization. These results, say the authors, reveal a new connection between ubiquitylation and phosphorylation pathways that stimulates the formation of the 14-3-3 signalling complex and could modulate a number of cellular processes.

• © 2013. Published by The Company of Biologists Ltd