FBXO38 is dispensable for PD-1 regulation.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2024-09-12 DOI:10.1038/s44319-024-00220-8

Nikol Dibus,Eva Salyova,Karolina Kolarova,Alikhan Abdirov,Michele Pagano,Ondrej Stepanek,Lukas Cermak

引用次数: 0

Abstract

SKP1-CUL1-F-box protein (SCF) ubiquitin ligases are versatile protein complexes that mediate the ubiquitination of protein substrates. The direct substrate recognition relies on a large family of F-box-domain-containing subunits. One of these substrate receptors is FBXO38, which is encoded by a gene found mutated in families with early-onset distal motor neuronopathy. SCFFBXO38 ubiquitin ligase controls the stability of ZXDB, a nuclear factor associated with the centromeric chromatin protein CENP-B. Loss of FBXO38 in mice results in growth retardation and defects in spermatogenesis characterized by deregulation of the Sertoli cell transcription program and compromised centromere integrity. Moreover, it was reported that SCFFBXO38 mediates the degradation of PD-1, a key immune-checkpoint inhibitor in T cells. Here, we have re-addressed the link between SCFFBXO38 and PD-1 proteolysis. Our data do not support the notion that SCFFBXO38 directly or indirectly controls the abundance and stability of PD-1 in T cells.

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FBXO38 对于 PD-1 的调控是必不可少的。

SKP1-CUL1-F-box 蛋白（SCF）泛素连接酶是介导蛋白质底物泛素化的多功能蛋白质复合体。底物的直接识别依赖于一个庞大的含 F-box 域的亚基家族。FBXO38 是这些底物受体之一，在早发性远端运动神经元病家族中，该基因发生了突变。SCFFBXO38 泛素连接酶控制着与中心染色质蛋白 CENP-B 相关的核因子 ZXDB 的稳定性。小鼠缺失 FBXO38 会导致生长迟缓和精子发生缺陷，其特征是 Sertoli 细胞转录程序失调和中心粒完整性受损。此外，有报道称 SCFFBXO38 能介导 T 细胞中关键免疫检查点抑制剂 PD-1 的降解。在这里，我们重新探讨了 SCFFBXO38 与 PD-1 蛋白解质之间的联系。我们的数据不支持 SCFFBXO38 直接或间接控制 T 细胞中 PD-1 的丰度和稳定性的观点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

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