Matters Arising: FBXO38 does not control PD-1 stability

Dibus, N.; Salyova, E.; Kolarova, K.; Pagano, M.; Stepanek, O.; Cermak, L.

doi:10.1101/2023.03.19.531556

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bioRxiv · 10.1101/2023.03.19.531556

Matters Arising: FBXO38 does not control PD-1 stability

Dibus, N.·Salyova, E.·Kolarova, K.·Pagano, M.·Stepanek, O.·Cermak, L.

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Abstract

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.

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Dibus, N., Salyova, E., Kolarova, K., Pagano, M., Stepanek, O., Cermak, L.. 2023-03-21. Matters Arising: FBXO38 does not control PD-1 stability. https://doi.org/10.1101/2023.03.19.531556

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