Targeting YWHAG protein: A unified therapeutic strategy against tumors or neurodegenerative diseases

Abstract

YWHAG is a subtype of the 14-3-3 protein family that regulates the transduction of multiple signaling pathways in cells, such as the phosphoinositide 3-kinase-protein kinase B (PI3K-AKT) and mitogen-activated protein kinase (MAPK) pathways, by recognizing and binding to specific phosphorylated target protein motifs. These signaling pathways are widely found to be abnormally activated or shut down in human diseases, such as cancer and neurodegenerative diseases. Different evidence has shown that the expression levels and functions of YWHAG in different tumors are not the same. Meanwhile, the potential functions of YWHAG in these diseases and its role in regulating abnormal signaling pathways are still unknown. Therefore, further exploration and research are needed to determine YWHAG’s core role in regulating signaling pathways and whether YWHAG can be a therapeutic target for diseases to develop corresponding drugs. This review will revisit the structure and function of YWHAG, elaborate on the newly identified YWHAG-interacting proteins in recent years, summarize the functions of YWHAG in cancer while comparing it with the homologous family member YWHAZ, explore the functions of YWHAG in neurodegenerative diseases, and present our perspectives on drug-screening strategies targeting YWHAG.

Keywords

14-3-3 protein / YWHAG / tumors / neurodegenerative / duality / targeted strategies

1 Authors contribution

Liu J, Jia S: Conceptualization, methodology.

Jing R: Visualization, writing-original draft.

Jia T, Lu Z: Visualization, writing-review & editing.

Liu J, ZhengR: Formal analysis.

Pan X: Visualization.

All authors have confirmed that they have reviewed the manuscript.

2 Conflicts of interest

Jing Liu is a Youth Editorial Board member of Ageing and Cancer Research & Treatment. The other authors declare no conflicts of interest.

3 Ethical approval

Not applicable.

4 Consent to participate

Not applicable.

5 Consent for publication

Not applicable.

6 Availability of data and materials

Not applicable.

Funding

This study was supported by grants from the National Natural Science Foundation of China (Grant No. 82060660 to J.L). J.L are supported by the Yunnan Revitalization Talent Support Program Young Talent Project (XDYC-QNRC-2022-0285).

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