骨骼是一种活生生的、复杂的、动态的组织，为身体提供运动和保护。它还执行造血和矿物质稳态。骨肉瘤 (OS)、尤文肉瘤 (ES) 和软骨肉瘤 (CS) 是原发性骨癌。 OS 和 ES 主要发生在年轻人中，CS 通常发生在成年人中。泛素化调节许多细胞过程。去泛素化酶 (DUB) 将泛素分子从泛素标记的底物上分离出来，改变泛素化蛋白质的功能并通过各种信号通路调节蛋白质稳定性。蛋白质稳态和骨重塑都受到 UPS 的重要影响。最近，有一些关于 DUB 通过 NF-κB、Wnt/β-catenin、TRAF6、TGFβ、ERK1/2 和 PI3K/Akt 通路调节成骨细胞和破骨细胞参与骨稳态和各种骨疾病的报道。然而，DUBs 调节骨稳态功能仍处于起步阶段。在这里，我们总结了最近对 DUB 的一些鉴定，重点关注它们在骨癌进展中的作用。因此，该研究试图总结 DUB 表达水平作为骨癌驱动关键因素的关联，并提供关于 DUB 作为骨癌治疗关键药理学靶点的新见解。© 2024。作者，获得 Springer 独家许可Science Business Media, LLC，隶属于施普林格自然集团。

Bone is a living, intricate, and dynamic tissue providing locomotion and protection of the body. It also performs hematopoiesis and mineral homeostasis. Osteosarcoma (OS), Ewing sarcoma (ES), and chondrosarcoma (CS) are primary bone cancers. OS and ES mostly develop in younger individuals, and CS generally develops in adults. Ubiquitination regulates numerous cellular processes. The deubiquitinating enzymes (DUBs) detach the ubiquitin molecules from the ubiquitin labeled substrate, altering ubiquitinated protein functions and regulating protein stability via various signaling pathways. Protein homeostasis and bone remodeling are both crucially influenced by the UPS. Recently, there have been several reports on DUBs involved in bone homeostasis and various bone disorders through the regulation of osteoblasts and osteoclasts via NF-κB, Wnt/β-catenin, TRAF6, TGFβ, ERK1/2, and PI3K/Akt pathways. However, DUBs regulating function in bone homeostasis is still in its infancy. Here, we summarized several recent identifications on DUBs, with a focus on their role in bone cancer progression. Therefore, the study attempts to summarize association with the expression level of DUBs as key factors driving bone cancers and also provide new insights on DUBs as key pharmacologic targets for bone cancer therapeutics.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.