Valosin-Containing Protein (VCP)/p97: A Prognostic Biomarker and Therapeutic Target in Cancer.

Valosin-Containing Protein (VCP)/p97: A Prognostic Biomarker and Therapeutic Target in Cancer.
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DOI:
10.3390/ijms221810177
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发表时间:
2021-09-21
影响因子:
5.6
通讯作者:
Budillon A
Budillon A
中科院分区:
生物学2区
文献类型:
--
作者:
Costantini S;Capone F;Polo A;Bagnara P;Budillon A

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含 Valosin 的蛋白 (VCP)/p97 是 AAA+ ATPase 家族的成员,是一种分子伴侣,通过与膜接头(核蛋白定位蛋白 4 (NPL4)、p47 和泛素调节 X (UBX) 结构域含有蛋白 1 (UBXD1))结合而招募到内质网 (ER) 膜,参与 ER 相关蛋白降解 (ERAD)。然而,VCP/p97 与许多辅助因子相互作用,参与对癌细胞存活和侵袭至关重要的不同细胞过程。事实上,据报道,VCP/p97 在许多癌症类型中过度表达,并被认为是潜在的癌症生物标志物和治疗靶点。本综述总结了VCP/p97在不同癌症中的作用以及具有治疗潜力的小分子抑制剂的发现进展,重点关注与癌症相关的VCP突变在抑制剂耐药机制中面临的挑战。
Valosin-containing protein (VCP)/p97, a member of the AAA+ ATPase family, is a molecular chaperone recruited to the endoplasmic reticulum (ER) membrane by binding to membrane adapters (nuclear protein localization protein 4 (NPL4), p47 and ubiquitin regulatory X (UBX) domain-containing protein 1 (UBXD1)), where it is involved in ER-associated protein degradation (ERAD). However, VCP/p97 interacts with many cofactors to participate in different cellular processes that are critical for cancer cell survival and aggressiveness. Indeed, VCP/p97 is reported to be overexpressed in many cancer types and is considered a potential cancer biomarker and therapeutic target. This review summarizes the role of VCP/p97 in different cancers and the advances in the discovery of small-molecule inhibitors with therapeutic potential, focusing on the challenges associated with cancer-related VCP mutations in the mechanisms of resistance to inhibitors.
定量相互作用映射显示ASPL中的扩展UBX结构域破坏了功能性p97六聚体。
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