Matters Arising: FBXO38 does not control PD-1 stability

SKP1-CUL1-F-box protein (SCF) ubiquitin ligases are versatile protein complexes that mediate the ubiquitination of substrates, which are recognized by their F-box-domain- containing subunits1. One of these substrate receptors is FBXO38. Its gene has been found to be mutated in several families with early-onset distal hereditary motor neuronopathy2. SCFFBXO38 ubiquitin ligase controls the stability of ZXDB, a nuclear factor associated with the centromeric chromatin protein CENP-B3. Moreover, the loss of FBXO38 results in growth retardation and defect in spermatogenesis characterized by deregulation of the Sertoli cell transcription program and centromere integrity4. A report by Meng et al. proposed that SCFFBXO38 regulates the protein levels of the PD-1 inhibitory receptor (also known as CD279, PDCD1) in T cells5. Here, we have re-addressed the conclusions by Meng et al. using Fbxo38KO/KO mice and cell systems. We have found no evidence indicating that FBXO38 controls the abundance and stability of PD-1.