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FOXO3a-interacting proteins’ involvement in cancer: a review

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Abstract

Due to its role in apoptosis, differentiation, cell cycle arrest, and DNA damage repair in stress responses (oxidative stress, hypoxia, chemotherapeutic drugs, and UV irradiation or radiotherapy), FOXO3a is considered a key tumor suppressor that determines radiotherapeutic and chemotherapeutic responses in cancer cells. Mutations in the FOXO3a gene are rare, even in cancer cells. Post-translational regulations are the main mechanisms for inactivating FOXO3a. The subcellular localization, stability, transcriptional activity, and DNA binding affinity for FOXO3a can be modulated via various post-translational modifications, including phosphorylation, acetylation, and interactions with other transcriptional factors or regulators. This review summarizes how proteins that interact with FOXO3a engage in cancer progression.

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Abbreviations

TF:

Transcription factor

FH:

Forkhead

DBD:

DNA binding domain

H1:

Helix 1

S1:

Strand 1

IDRs:

Intrinsically disordered regions

CRs:

Conserved regions

NLS:

Nuclear localization sequences

TAD:

Trans-activation domain

NES:

Nuclear export sequence

OS:

Oxidative stress

PTMs:

Post-translational modifications

TRs:

Transcriptional regulators

NSCLC:

Non-small cell lung cancer

SGK:

Serum and glucocorticoid-inducible kinase

IKK:

IκB kinase

UPD:

Ubiquitin–proteasome degradation

Aur-A:

Aurora-A

SKP2:

S-phase kinase-associated protein 2

AMPK:

AMP-activated protein kinase

MST1:

Mammalian Sterile 20-like kinase 1

BC:

Breast cancer

EMT:

Epithelial-mesenchymal transition

CRC:

Colorectal cancer

FHRE:

FH transcriptional response element

CARM1:

Coactivator-Associated Arginine Methyltransferase1

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Acknowledgements

Not applicable.

Funding

This research was supported by the Natural Science Foundation of Shandong Province (ZR2022MC125, ZR2022LZL006) and Yantai Nanshan University Youth Fund (NS2022Q14).

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Authors and Affiliations

  1. Health College, Yantai Nanshan University, Yantai, 265700, Shandong, China

    Zhiqiang Dong, Zongming Guo, Hui Li, Dequan Han, Wei Xie, Shaoning Cui, Wei Zhang & Shuhong Huang

  2. Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250062, Shandong, China

    Zhiqiang Dong & Shuhong Huang

  3. School of Clinical and Basic Medical Sciences, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250062, Shandong, China

    Shuhong Huang

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  1. Zhiqiang Dong
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ZD am mainly responsible for collecting literature, writing articles and sorting out materials. ZG, HL and DH were involved in the analysis of literature. WX and SC were involved in the production of pictures. WZ and SH were the creators and leaders of the project and directed thesis writing. All the authors have read and approved the final version of this review.

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Dong, Z., Guo, Z., Li, H. et al. FOXO3a-interacting proteins’ involvement in cancer: a review. Mol Biol Rep 51, 196 (2024). https://doi.org/10.1007/s11033-023-09121-w

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