Modular cullin-RING E3 ubiquitin ligases (CRLs) use substrate binding adaptor 
proteins to specify target ubiquitylation. Many of the ~200 human CRL adaptor 
proteins remain poorly studied due to a shortage of efficient methods to 
identify biologically relevant substrates. Here, we report the development of 
parallel adaptor capture (PAC) proteomics and its use to systematically identify 
candidate targets for the leucine-rich repeat family of F-box proteins (FBXLs) 
that function with SKP1-CUL1-F-box protein (SCF) E3s. In validation experiments, 
we identify the unstudied F-box protein FBXL17 as a regulator of the NFR2 
oxidative stress pathway. We demonstrate that FBXL17 controls the transcription 
of the NRF2 target HMOX1 via turnover of the transcriptional repressor BACH1 in 
the absence or presence of extrinsic oxidative stress. This work identifies a 
role for SCF(FBXL17) in controlling the threshold for NRF2-dependent gene 
activation and provides a framework for elucidating the functions of CRL adaptor 
proteins.