Members of the Bric-a-Brac/Tramtrack/Broad Complex (BTB) family direct the selective ubiquitylation of proteins following their assembly into Cullin3-based ubiquitin ligases. Here, we describe a subfamily of nucleus-localized BTB proteins encoded by the LIGHT-RESPONSE BTB1 (LRB1) and LRB2 loci in Arabidopsis (Arabidopsis thaliana) that strongly influences photomorphogenesis. Whereas single lrb1 and lrb2 mutants are relatively normal phenotypically, double mutants are markedly hypersensitive to red light, but not to far-red or blue light, and are compromised in multiple photomorphogenic processes, including seed germination, cotyledon opening and expansion, chlorophyll accumulation, shade avoidance, and flowering time. This red light hypersensitivity can be overcome by eliminating phytochrome B (phyB) and phyD, indicating that LRB1/2 act downstream of these two photoreceptor isoforms. Levels of phyB/D proteins but not their messenger RNAs are abnormally high in light-grown lrb1 lrb2 plants, implying that their light-dependent turnover is substantially dampened. Whereas other red light-hypersensitive mutants accumulate phyA protein similar to or higher than the wild type in light, the lrb1 lrb2 mutants accumulate less, suggesting that LRB1/2 also positively regulate phyA levels in a phyB/D-dependent manner. Together, these data show that the BTB ubiquitin ligases assembled with LRB1/2 function redundantly as negative regulators of photomorphogenesis, possibly by influencing the turnover of phyB/D.The selective breakdown of short-lived regulatory proteins is a key feature of many signal transduction pathways, thus providing a mechanism to enhance or quench output when repressors or activators are the respective targets. In eukaryotes, much of this specific turnover is mediated by the ubiquitin/26S proteasome system (UPS; Smalle and Vierstra, 2004;Kerscher et al., 2006). Here, polymeric chains of ubiquitin (Ub) are covalently attached to proteins destined for degradation via an ATP-dependent, E1-E2-E3 conjugation cascade. These poly-Ub moieties are then recognized by the 26S proteasome, a 2.5-MD protease complex that directs proteolysis of the target with the concomitant release of the Ub moieties for reuse. The specificity of the UPS resides mainly in the E3 Ub protein ligases that choose appropriate proteins for ubiquitylation. E3s recognize structural motifs in the target and then catalyze an isopeptide linkage between the C-terminal Gly of Ub and an accessible lysl «-amino group in the target, using an E2-Ub thioester intermediate as the donor. Substantial variations in E3 sequence and organization generate the wide range of specificities needed to handle the myriad of likely UPS substrates (Vierstra, 2009). In Arabidopsis (Arabidopsis thaliana), for example, phylogenetic analyses have identified well over 1,500 possible E3 genes, with genetic studies on a few implying that many have unique substrates (Vierstra, 2009;Hua and Vierstra, 2011).The multisubunit Cullin-RING Ligases (CRLs) are a highly polymorphic col...