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通过PP2A修饰剂改变癌症中的磷酸化作用。

Altering phosphorylation in cancer through PP2A modifiers.

作者信息

Johnson Hannah, Narayan Satya, Sharma Arun K

机构信息

Department of Pharmacology, Penn State Cancer Institute, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA.

Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL, 32610, USA.

出版信息

Cancer Cell Int. 2024 Jan 6;24(1):11. doi: 10.1186/s12935-023-03193-1.

Abstract

Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase integral to the regulation of many cellular processes. Due to the deregulation of PP2A in cancer, many of these processes are turned toward promoting tumor progression. Considerable research has been undertaken to discover molecules capable of modulating PP2A activity in cancer. Because PP2A is capable of immense substrate specificity across many cellular processes, the therapeutic targeting of PP2A in cancer can be completed through either enzyme inhibitors or activators. PP2A modulators likewise tend to be effective in drug-resistant cancers and work synergistically with other known cancer therapeutics. In this review, we will discuss the patterns of PP2A deregulation in cancer, and its known downstream signaling pathways important for cancer regulation, along with many activators and inhibitors of PP2A known to inhibit cancer progression.

摘要

蛋白磷酸酶2A(PP2A)是一种丝氨酸/苏氨酸磷酸酶,对许多细胞过程的调节至关重要。由于癌症中PP2A的失调,其中许多过程都转向促进肿瘤进展。已经开展了大量研究来发现能够调节癌症中PP2A活性的分子。由于PP2A在许多细胞过程中具有巨大的底物特异性,因此可以通过酶抑制剂或激活剂来实现癌症中PP2A的治疗靶向。PP2A调节剂同样倾向于在耐药性癌症中有效,并与其他已知的癌症治疗药物协同作用。在这篇综述中,我们将讨论癌症中PP2A失调的模式、其已知的对癌症调节重要的下游信号通路,以及许多已知可抑制癌症进展的PP2A激活剂和抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74a8/10770906/f1f929f2ce21/12935_2023_3193_Fig1_HTML.jpg

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