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Review

RING finger protein family in leukemia (Review)

  • Authors:
    • Ye Wang
    • Yue Zhao
    • Jihong Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110022, P.R. China, Hematology Laboratory, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110022, P.R. China
  • Article Number: 17
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    Published online on: October 29, 2025
       https://doi.org/10.3892/mmr.2025.13727
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Abstract

Ubiquitination is a highly conserved and indispensable post‑translational modification in eukaryotic systems, serving as a fundamental regulatory mechanism for protein homeostasis and function. The RING finger protein (RNF) family, distinguished by their characteristic RING domains, constitute a major class of E3 ubiquitin ligases that orchestrate substrate specificity and ubiquitin transfer, thereby modulating diverse cellular processes. Accumulating evidence over the past decade has firmly established the pivotal involvement of RNF proteins in various pathological conditions, including infectious diseases, autoimmune disorders and malignancies. The present review systematically examined the mechanistic contributions of RNF family members to leukemogenesis, with particular emphasis on their regulatory roles in disease progression and therapeutic resistance. By synthesizing current knowledge, it highlighted the emerging potential of RNF proteins as both prognostic biomarkers and therapeutic targets in leukemia and advocate for the development of selective RNF‑targeting inhibitors as a promising strategy for leukemia treatment.
View Figures

Figure 1

Classification of the RNF family,
along with the structure and members of its subfamilies. RING,
really interesting new gene; BB, B-box; CC, coiled-coil; IBR,
in-between-RING domain; TM, transmembrane; PA, protease associated;
C2HC, Cys2-His-Cys zinc finger; C2H2, Cys2-His2 zinc fingers; UIM,
ubiquitin interacting motif.

Figure 2

Members of the RNF family play a
critical role in the regulation of leukemia development through
various pathways. Specifically, TRIM14, TRIM22, TRIM37, TRIM24,
TRIM31, TRIM10 and RNF144B influence the proliferation and
apoptosis of leukemia cells by modulating the PI3K/AKT,
Wnt/β-catenin and NF-κB signaling pathways. Additionally, proteins
such as MARCH5, PARK2, HOIP and RNF217 are implicated in altering
the properties of leukemia cells through their actions on
mitochondria. Furthermore, RNF138, PARC, TRIM13, MARCH1 and TRIM31,
among others, affect leukemia cell differentiation, cell cycle
progression and colony formation, as well as the homeostasis of
hematopoietic stem cells and the initiation of leukemia by
modulating the activities of C/EBPα, P53, CCNA1, CD98 and CDK8,
respectively. HoxA10 enhances the transcription of Triad1, while
elevated Triad1 expression counteracts the effects of overexpressed
HoxA10 on bone marrow proliferation, with Triad1 influencing AML
prognosis by interfering with RTK termination during stress-induced
granulopoiesis. Moreover, miR-137 suppresses the pro-oncogenic
effects of TRIM25 in leukemia, TRIM32 serves as a coactivator of
RARα-mediated transcription and promotes APL cell differentiation
and TRIM33 inhibits apoptosis by disrupting enhancer-mediated
activation of Bim transcription. Ub, ubiquitin; PTEN, phosphatase
and tensin homolog; GSK-3β, glycogen synthase kinase-3β; C/EBPα,
CCAAT/enhancer binding protein α; CSF3α, colony-stimulating factor
3α; CDK8, cyclin-dependent kinase 8; NPMc, nucleophosmin;
FANCA-FANCC, Fanconi anemia proteins complex; PBX1, pre-B-cell
leukemia transcription factor 1; HOXA10, homeobox A10; HAX1,
HS1-associated protein X-1; OPA1, optic atrophy 1; MFN2, mitofusin
2; IL6Rα, interleukin-6 receptor α chain; RTK, receptor tyrosine
kinases; CHAF1B, chromatin assembly factor 1B; CCNA1, cell cycle
gene cyclin A1; Bim, a Bcl-2 homology 3-only protein; PU.1, a
member of transcription factors.
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Copy and paste a formatted citation
Spandidos Publications style
Wang Y, Zhao Y and Zhang J: RING finger protein family in leukemia (Review). Mol Med Rep 33: 17, 2026.
APA
Wang, Y., Zhao, Y., & Zhang, J. (2026). RING finger protein family in leukemia (Review). Molecular Medicine Reports, 33, 17. https://doi.org/10.3892/mmr.2025.13727
MLA
Wang, Y., Zhao, Y., Zhang, J."RING finger protein family in leukemia (Review)". Molecular Medicine Reports 33.1 (2026): 17.
Chicago
Wang, Y., Zhao, Y., Zhang, J."RING finger protein family in leukemia (Review)". Molecular Medicine Reports 33, no. 1 (2026): 17. https://doi.org/10.3892/mmr.2025.13727
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Y, Zhao Y and Zhang J: RING finger protein family in leukemia (Review). Mol Med Rep 33: 17, 2026.
APA
Wang, Y., Zhao, Y., & Zhang, J. (2026). RING finger protein family in leukemia (Review). Molecular Medicine Reports, 33, 17. https://doi.org/10.3892/mmr.2025.13727
MLA
Wang, Y., Zhao, Y., Zhang, J."RING finger protein family in leukemia (Review)". Molecular Medicine Reports 33.1 (2026): 17.
Chicago
Wang, Y., Zhao, Y., Zhang, J."RING finger protein family in leukemia (Review)". Molecular Medicine Reports 33, no. 1 (2026): 17. https://doi.org/10.3892/mmr.2025.13727
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