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

Hao Liu1, Zhi-Liang Jiang2,3, Yi Liu4,5

  • 1Department of Medicine, Queen Mary School, Nan Chang University, Nanchang, Jiangxi 330031, P.R. China.

Oncology Letters
|November 21, 2025
PubMed

Insights

PEST-nuclear proteins (PEST-NPs) are crucial in ovarian cancer (OC) development and platinum resistance. Understanding their post-translational modifications (PTMs) offers new diagnostic and therapeutic strategies for this deadly gynecological malignancy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Ovarian cancer (OC) is a highly lethal gynecological malignancy with poor survival rates, largely due to late diagnosis and acquired platinum resistance.
  • Platinum-based chemotherapy is a standard treatment, but resistance remains a major clinical hurdle, necessitating novel therapeutic targets and biomarkers.
  • The PEST amino acid sequence (Proline, Glutamic acid, Serine, Threonine) is a degradation motif that regulates nuclear protein (NP) stability, localization, and activation via post-translational modifications (PTMs).

Purpose of the Study:

  • To review the critical roles of PEST sequence-enriched nuclear proteins (PEST-NPs) in ovarian cancer initiation, progression, and chemoresistance.
  • To elucidate how PTMs of PEST domains influence the stability, activation, and intracellular localization of PEST-NPs in OC.
  • To identify challenges and opportunities for translating PEST-NP research into clinical diagnostics and therapeutics for OC.

Main Methods:

  • Literature review focusing on PEST-NPs and their PTMs in ovarian cancer.
  • Analysis of the functional impact of PEST-NPs on cancer metabolism, immunity, and transcription.
  • Synthesis of current knowledge on PEST-NP regulation and its clinical implications.

Main Results:

  • PEST-NPs function as either oncogenes or tumor suppressors, significantly impacting OC pathogenesis.
  • PTMs of PEST domains are key regulators of PEST-NP stability, activation, and localization, driving OC progression and chemoresistance.
  • Dysregulation of PEST-NPs contributes to OC initiation, metastasis, and resistance to platinum-based chemotherapy.

Conclusions:

  • PEST-NPs and their PTMs are pivotal in ovarian cancer development and platinum resistance, representing promising therapeutic targets.
  • Further research into PEST-NP biology and PTMs is essential for developing effective OC diagnostics and therapies.
  • Translating findings on PEST-NPs from the laboratory to clinical application holds significant potential for improving patient outcomes in ovarian cancer.
Keywords:
PCNPPEST sequencenuclear proteinsovarian cancertherapeutics

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