The ArabidopsisALF4 protein is a regulator of SCF E3 ligases

The cullin-RING E3 ligases (CRLs) regulate diverse cellular processes in all eukaryotes. CRL activity is controlled by several proteins or protein complexes, including NEDD8, CAND1, and the CSN. Recently, a mammalian protein called Glomulin (GLMN) was shown to inhibit CRLs by binding to the RING BOX (RBX1) subunit and preventing binding to the ubiquitin-conjugating enzyme. Here, we show that ArabidopsisABERRANT LATERAL ROOT FORMATION4 (ALF4) is an ortholog of GLMN. The alf4 mutant exhibits a phenotype that suggests defects in plant hormone response. We show that ALF4 binds to RBX1 and inhibits the activity of SCFTIR1, an E3 ligase responsible for degradation of the Aux/IAA transcriptional repressors. In vivo, the alf4 mutation destabilizes the CUL1 subunit of the SCF. Reduced CUL1 levels are associated with increased levels of the Aux/IAA proteins as well as the DELLA repressors, substrate of SCFSLY1. We propose that the alf4 phenotype is partly due to increased levels of the Aux/IAA and DELLA proteins. Synopsis ALF4, the Arabidopsis thaliana ortholog of the cullin-ring ubiquitin ligase regulator glomulin, stabilizes CUL1 in vivo, thereby decreasing the levels of Aux/IAA proteins and modulating the auxin hormone response. The ArabidopsisALF4 protein is an ortholog of human glomulin (GLMN). ALF4 binds to the RBX1 subunit of cullin-ring ligases and inhibits SCFTIR1 in vitro. Loss of ALF4 results in stabilization of the SCF substrates IAA7 and RGAin vivo. Global levels of ubiquitinated proteins are reduced in the alf4 mutant.