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Biology of PEST‑containing nuclear proteins as potential targets in ovarian cancer (Review)

  • Authors:
    • Hao Liu
    • Zhi-Liang Jiang
    • Yi Liu
    • Yong-Hao Zhu
    • Muhammad Usman Akbar
    • Saadullah Khattak
    • Zhendong Lu
    • Muhammad Babar Khawar
    • Yue Zhang
    • Umair Ali Khan Saddozai
    • Xin-Ying Ji
  • View Affiliations / Copyright

    Affiliations: Department of Medicine, Queen Mary School, Nan Chang University, Nanchang, Jiangxi 330031, P.R. China, Department of Clinical Medicine, School of Medicine, Henan University, Kaifeng, Henan 475004, P.R. China, Department of Medicine, School of Stomatology, Henan University, Kaifeng, Henan 475004, P.R. China, Department of Biochemistry, Gomal University, Dera Ismail Khan, Khyber Pakhtunkhwa 29111, Pakistan, Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Henan University, Kaifeng, Henan 475004, P.R. China, Department of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China, Department of Obstetrics and Gynecology, 988 Hospital of PLA, Zhengzhou, Henan 450000, P.R. China, Kaifeng Municipal Key Laboratory for Infection and Biosafety, Henan International Joint Laboratory of Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University College of Medicine, Kaifeng, Henan 475004, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 26
    |
    Published online on: November 7, 2025
       https://doi.org/10.3892/ol.2025.15379
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Abstract

Ovarian cancer (OC) is the deadliest gynecological malignancy, with a 5‑year survival rate of 47%, primarily due to late diagnosis and platinum resistance. Although patients with OC often exhibit an initial clinical response to platinum‑based chemotherapy, they typically develop resistance to platinum, posing a significant clinical challenge. Therefore, identifying effective biomarkers and potential therapeutic targets is critical. The PEST amino acid sequence, which comprises proline (P), glutamic acid (E), serine (S) and threonine (T), functions as a structural recognition motif for the cellular degradation machinery and modulates post‑translational modifications (PTMs) of nuclear proteins (NPs), regulating their activation, localization and stability. PEST sequence‑enriched NPs (PEST‑NPs) act as oncogenes or tumor suppressors and influence cancer metabolism, immunity and transcription, and are thus potential therapeutic targets. The present review highlighted the multifaceted roles of PEST‑NPs in types of OC, focusing on how PTMs of PEST domains mediate the activation, localization and stability of PEST‑NPs. PTMs regulate the stability, activation and intracellular localization of PEST‑NPs, thereby driving OC initiation, progression and chemoresistance. The present review also highlighted related hallenges and opportunities, including future research to facilitate the translation of PEST‑NP‑based OC diagnostics and therapies from the laboratory to the clinic. Future research insights will further support the development of diagnostic and therapeutic approaches for OC based on NPs, facilitating their translation from laboratory settings to applications.
View Figures

Figure 1

Multifaceted behaviors of the PEST
sequence and PEST-NPs. BMI, PCNP and P53 are involved in apoptosis
in ovarian cancer via interference with the oncogenic pathways of
PI3K/AKT, Wnt, and PI3K/AKT. By contrast, Myc and PTEN are involved
in proliferation through the oncogenic PI3K/Akt/mTOR and PI3K/Akt
pathways (By FigDraw). PEST, proline, glutamic acid, serine,
threonine; NPs, nuclear proteins; PCNP, PEST-containing NP; Bmi1,
BMI1 proto-oncogene, polycomb ring finger.

Figure 2

PEST sequence-containing
phosphorylated substrates are degraded by a complex of the proteins
Cdc34/Ubc3 and SCFs (By FigDraw). Cell division cycle; PEST,
proline, glutamic acid, serine and threonine; SCF, Skp1, cullin and
F-box protein; Ub, ubiquitin; Ubc, Ub-conjugating enzyme; Cdc, cell
division cycle.

Figure 3

Wnt signaling pathway activation and
the progression of ovarian cancer is facilitated by the interaction
of PCNP with β-catenin, which stabilizes PCNP and enhances the
expression of β-catenin in the nucleus (By FigDraw). PCNP,
PEST-containing nuclear protein; Ctnn-B, β-catenin; TCF/LEF, T-cell
factor/lymphoid enhancer factor; ZEB1, zinc finger E-box binding
homeobox 1; E-cadherin, epithelial cadherin.

Figure 4

Mechanisms of PEST-NPs in cancer
progression via PTMs and key signaling pathways. Summarization of
the interactions between PEST-NPs (p53, PTEN, Bmi1, c-Myc and PCNP)
and their key post-translational modifications (ubiquitination,
phosphorylation, acetylation, SUMOylation and O-GlcNAcylation),
which regulate protein stability, activation or subcellular
localization. These modifications further modulate downstream
signaling pathways (such as PI3K/Akt/mTOR, Wnt/β-catenin, Notch and
mitochondrial apoptosis) and contribute to cancer progression
phenotypes, including altered cell proliferation, apoptosis, stem
cell self-renewal, metabolism, epithelial-mesenchymal transition
and metastasis (By FigDraw). PEST, proline, glutamic acid, serine,
threonine; NPs, nuclear proteins; PCNP, PEST-containing NP; PTMs,
post-translational modifications; Bmi1, BMI1 proto-oncogene,
polycomb ring finger; EMT, epithelial-mesenchymal transition.
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Copy and paste a formatted citation
Spandidos Publications style
Liu H, Jiang Z, Liu Y, Zhu Y, Akbar MU, Khattak S, Lu Z, Khawar MB, Zhang Y, Saddozai UA, Saddozai UA, et al: Biology of PEST‑containing nuclear proteins as potential targets in ovarian cancer (Review). Oncol Lett 31: 26, 2026.
APA
Liu, H., Jiang, Z., Liu, Y., Zhu, Y., Akbar, M.U., Khattak, S. ... Ji, X. (2026). Biology of PEST‑containing nuclear proteins as potential targets in ovarian cancer (Review). Oncology Letters, 31, 26. https://doi.org/10.3892/ol.2025.15379
MLA
Liu, H., Jiang, Z., Liu, Y., Zhu, Y., Akbar, M. U., Khattak, S., Lu, Z., Khawar, M. B., Zhang, Y., Saddozai, U. A., Ji, X."Biology of PEST‑containing nuclear proteins as potential targets in ovarian cancer (Review)". Oncology Letters 31.1 (2026): 26.
Chicago
Liu, H., Jiang, Z., Liu, Y., Zhu, Y., Akbar, M. U., Khattak, S., Lu, Z., Khawar, M. B., Zhang, Y., Saddozai, U. A., Ji, X."Biology of PEST‑containing nuclear proteins as potential targets in ovarian cancer (Review)". Oncology Letters 31, no. 1 (2026): 26. https://doi.org/10.3892/ol.2025.15379
Copy and paste a formatted citation
x
Spandidos Publications style
Liu H, Jiang Z, Liu Y, Zhu Y, Akbar MU, Khattak S, Lu Z, Khawar MB, Zhang Y, Saddozai UA, Saddozai UA, et al: Biology of PEST‑containing nuclear proteins as potential targets in ovarian cancer (Review). Oncol Lett 31: 26, 2026.
APA
Liu, H., Jiang, Z., Liu, Y., Zhu, Y., Akbar, M.U., Khattak, S. ... Ji, X. (2026). Biology of PEST‑containing nuclear proteins as potential targets in ovarian cancer (Review). Oncology Letters, 31, 26. https://doi.org/10.3892/ol.2025.15379
MLA
Liu, H., Jiang, Z., Liu, Y., Zhu, Y., Akbar, M. U., Khattak, S., Lu, Z., Khawar, M. B., Zhang, Y., Saddozai, U. A., Ji, X."Biology of PEST‑containing nuclear proteins as potential targets in ovarian cancer (Review)". Oncology Letters 31.1 (2026): 26.
Chicago
Liu, H., Jiang, Z., Liu, Y., Zhu, Y., Akbar, M. U., Khattak, S., Lu, Z., Khawar, M. B., Zhang, Y., Saddozai, U. A., Ji, X."Biology of PEST‑containing nuclear proteins as potential targets in ovarian cancer (Review)". Oncology Letters 31, no. 1 (2026): 26. https://doi.org/10.3892/ol.2025.15379
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