Previous studies demonstrated that activating transcription factor 4 (ATF4) and proto‐oncogene c‐Myc serve as substrates of CRL ubiquitin ligase and transcriptional activators of Noxa in a cell line‐dependent manner.12, 19, 45, 46 Therefore, ATF4 and c‐Myc were chosen for their CRL substrates identities as potential transcription factors for MLN4924‐induced Noxa activation in HNSCC.19, 45 As shown in Figure 5A, MLN4924 treatment induced the accumulation of both c‐Myc and ATF4. Here, ATF4 is linked to head and neck squamous cell carcinoma.