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Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
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Phosphorylation-Dependent Stabilization of Collaborator of ARF (CARF) Suppresses Lymphoma Cell Proliferation

Li Qu1, Zhuang Wei2, Shuting Zhou1

  • 1Joint Center for Single Cell Biology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|July 6, 2025
PubMed

Insights

Altering phosphorylation of Collaborator of ARF (CARF) and plant Kip-Related Protein6 (KRP6) inhibits lymphoma cell proliferation. This suggests targeting phosphorylation sites on these proteins for precise cancer therapy.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Uncontrolled cell proliferation drives cancer, making cell cycle regulation a key therapeutic strategy.
  • Phosphorylation of proteins is crucial in cancer initiation, metastasis, and progression.
  • Identifying critical phosphorylation sites is essential for developing targeted cancer therapies.

Purpose of the Study:

  • To investigate the role of Collaborator of ARF (CARF) in lymphoma prognosis and survival.
  • To explore the function of conserved phosphorylation sites in CARF and plant Kip-Related Protein6 (KRP6) in cell cycle regulation.
  • To evaluate the therapeutic potential of targeting CARF phosphorylation in B-cell lymphoma.

Main Methods:

  • Pan-cancer analysis to assess CARF association with lymphoma patient prognosis.
  • Comparative analysis of mammalian CARF and plant KRP6, including phosphorylation site identification.
  • In vitro assays using B-cell lymphoma cell lines and in vivo studies with a mouse xenograft model to evaluate CARF variants.

Main Results:

  • CARF is strongly associated with prognosis and survival in lymphoma patients.
  • Conserved phosphorylation sites at serine 316 and 356 in CARF, analogous to KRP6 serines 75 and 109, regulate its function.
  • A non-phosphorylated CARF variant significantly inhibited B-cell lymphoma cell proliferation and tumor formation compared to wild-type CARF.

Conclusions:

  • Phosphorylation at conserved sites in CARF critically regulates B-cell lymphoma cell proliferation.
  • Targeting phosphorylation of CARF offers a promising strategy for precise lymphoma treatment.
  • The findings suggest potential cross-species bioengineering applications for phosphorylation-modified proteins in cancer therapy.
Keywords:
CARF (Collaborator of ARF)cell divisionlymphomaphosphorylationprecise therapeutics

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