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Ribosome‑binding protein 1: A multidimensional regulator of cancer progression and a novel target for precision therapy (Review)

  • Authors:
    • Ho Huang
    • Jia Ouyang
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    Affiliations: Peking University Health Science Center, Peking University, Beijing 100044, P.R. China, Department of Neurosurgery, Peking University People's Hospital, Beijing 100044, P.R. China
    Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 5
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    Published online on: October 23, 2025
       https://doi.org/10.3892/ol.2025.15358
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Abstract

Ribosome‑binding protein 1 (RRBP1), a core regulator of endoplasmic reticulum‑ribosome interactions, serves key roles in the development and progression of various cancer types by coordinating protein synthesis and organelle dynamic interactions. RRBP1 regulates the unfolded protein response by stabilizing glucose‑regulated protein 78 and it enhances cancer cell adaptation to endoplasmic reticulum stress and chemotherapy. The stability of RRBP1 is regulated by N6‑methyladenosine modification by methyltransferase‑like 3 and deubiquitination by ubiquitin‑specific processing protease 35. Furthermore, RRBP1 drives cellular anti‑apoptosis mechanisms by activating pro‑survival pathways such as TGF‑β1/SMAD, PI3K/AKT and Notch or binding cyclic RNAs. By contrast, aberrant activation of kinase function and deubiquitination pathways by RRBP1 fusion genes [RRBP1‑anaplastic lymphoma kinase, RRBP1‑Raf1 proto‑oncogene, serine/threonine kinase and RRBP1‑ubiquitin specific peptidase 6] exacerbates malignant progression. Furthermore, the pleiotropic regulation of RRBP1 in neurodegeneration, cardiovascular homeostasis and bone metabolism highlights its environment‑dependent functions. The present review identified the multidimensional regulatory network of RRBP1 in cancer and non‑cancer systems to enhance the understanding of its molecular mechanism, demonstrated its broad regulatory value and potentially provided a key entry point to analyze the disease and develop precision therapies.
View Figures

Figure 1

Schematic of RRBP1 gene
structure and predicted 3D protein conformation. (A) RRBP1
gene from Ensembl, revealing various splicing variants, coding and
non-coding transcripts and regulatory features. The default
transcript (MANE Select) is RRBP1-204. Visualization adapted from
the Ensembl Genome Browser (RRBP1, release 114, EMBL-EBI,
http://www.ensembl.org). (B) Predicted protein
structure of RRBP1. The color gradient from blue to yellow
indicates the predicted local distance difference test confidence
score (blue, high confidence; yellow/orange, low confidence). The
structure reveals the characteristic long α-helical segments and
coiled-coil architecture of RRBP1. Predicted protein structure from
the AlphaFold Protein Structure Database (UniProt ID, Q9P2E9,
DeepMind and EMBL-EBI, http://alphafold.ebi.ac.uk). RRBP1, ribosome-binding
protein 1; EMBL-EBI, European Molecular Biology Laboratory-European
Bioinformatics Institute; MANE, matched annotation.

Figure 2

Pan-cancer landscape of RRBP1 genomic
alterations (cBioPortal database). (A) RRBP1 gene OncoPrint
visualization. An asterisk (*) indicates that not all samples are
profiled. (B) RRBP1 gene mutation overview in various cancer types.
CNA, copy number alteration; TCGA, The Cancer Genome Atlas; RRBP1,
ribosome-binding protein 1.

Figure 3

RRBP1 adapts to ERS through the UPR
and enhancement of self-stabilization. RRBP1 upregulates GRP78
expression by stabilizing GRP78 mRNA and regulates ATF6 mRNA to
stabilize ATF6 for participation in the UPR. In addition, RRBP1
inhibits degradation pathways through METTL3-mediated m6A
methylation and USP35-mediated deubiquitination, thus enhancing
self-stability and promoting adaptive stress signaling. RRBP1,
ribosome-binding protein 1; Ub, ubiquitin; UPR, unfolded protein
response; ERS, endoplasmic reticulum stress; GRP78,
glucose-regulated protein 78; ROS, reactive oxygen species; METTL3,
methyltransferase-like 3; USP35, ubiquitin-specific processing
protease 35; ATF6, activating transcription factor 6; m6A,
N6-methyladenine; PERK, protein kinase R-like endoplasmic reticulum
kinase.

Figure 4

RRBP1 promotes anti-apoptosis through
different signaling pathways, gene fusions and interactions with
circRNAs. RRBP1 activates various signaling pathways, thereby
promoting tumor cell proliferation and anti-apoptosis. It also
inactivates Hippo signaling and activates pro-survival and
anti-apoptotic genes. In addition, RRBP1 activates kinase
function through gene fusion (ALK, RAF1 and USP6),
promotes MAPK and other pathways and upregulates deubiquitination.
Furthermore, in the interaction between RRBP1 and circRNAs, binding
of RRBP1 to hsa_circ_0004085 stabilizes GRP78 and enhances cellular
adaptation to ERS. By contrast, circVPS13C inhibits the binding of
RRBP1 to IFITM1 mRNA by competitively binding RRBP1; subsequently,
degradation of IFITM1 mRNA leads to notable downregulation of its
protein expression level and further inhibits apoptosis. RRBP1,
ribosome-binding protein 1; YAP1, Yes-associated protein 1; ALK,
anaplastic lymphoma kinase; GRP78, glucose-regulated protein 78;
ERS, endoplasmic reticulum stress; IFITM1, interferon-induced
transmembrane protein 1; circRNA, circular RNA; hsa, Homo
sapiens; TEAD, transcription enhancement associated domain
family members; MST1/2, mammalian sterile 20-like kinase 1/2;
LATS1/2, large tumor suppressor 1/2.

Figure 5

Survival analysis of RRBP1
alterations in stomach adenocarcinoma and skin cutaneous melanoma
(cBioPortal database). (A-C) Kaplan-Meier curves in patients with
stomach adenocarcinoma with (red) or without (blue) RRBP1
alterations. (A) Overall survival. (B) Disease-specific survival.
(C) Progression-free survival. (D-F) Kaplan-Meier curves in
patients with skin cutaneous melanoma. (D) Overall survival. (E)
Disease-specific survival. (F) Progression-free survival. RRBP1,
ribosome-binding protein 1.

Figure 6

RRBP1 expression in various human
organs and associated cancer types. Schematic diagram demonstrating
RRBP1-associated cancer types and representative molecular
mechanisms or keywords. Blue circles indicate tumor-promoting
roles, whereas green circles indicate tumor-suppressive roles.
‘Others’ include cancer types without specific organ illustration
(created in FigDraw). RRBP1, ribosome-binding protein 1, circRNA,
circular RNA; E2F1, E2F transcription factor 1; IRES, internal
ribosome entry site; USP35, ubiquitin-specific processing protease
35; m6A, N6-methyladenine; ALK, anaplastic lymphoma
kinase; METTL3, methyltransferase-like 3.
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Copy and paste a formatted citation
Spandidos Publications style
Huang H and Ouyang J: Ribosome‑binding protein 1: A multidimensional regulator of cancer progression and a novel target for precision therapy (Review). Oncol Lett 31: 5, 2026.
APA
Huang, H., & Ouyang, J. (2026). Ribosome‑binding protein 1: A multidimensional regulator of cancer progression and a novel target for precision therapy (Review). Oncology Letters, 31, 5. https://doi.org/10.3892/ol.2025.15358
MLA
Huang, H., Ouyang, J."Ribosome‑binding protein 1: A multidimensional regulator of cancer progression and a novel target for precision therapy (Review)". Oncology Letters 31.1 (2026): 5.
Chicago
Huang, H., Ouyang, J."Ribosome‑binding protein 1: A multidimensional regulator of cancer progression and a novel target for precision therapy (Review)". Oncology Letters 31, no. 1 (2026): 5. https://doi.org/10.3892/ol.2025.15358
Copy and paste a formatted citation
x
Spandidos Publications style
Huang H and Ouyang J: Ribosome‑binding protein 1: A multidimensional regulator of cancer progression and a novel target for precision therapy (Review). Oncol Lett 31: 5, 2026.
APA
Huang, H., & Ouyang, J. (2026). Ribosome‑binding protein 1: A multidimensional regulator of cancer progression and a novel target for precision therapy (Review). Oncology Letters, 31, 5. https://doi.org/10.3892/ol.2025.15358
MLA
Huang, H., Ouyang, J."Ribosome‑binding protein 1: A multidimensional regulator of cancer progression and a novel target for precision therapy (Review)". Oncology Letters 31.1 (2026): 5.
Chicago
Huang, H., Ouyang, J."Ribosome‑binding protein 1: A multidimensional regulator of cancer progression and a novel target for precision therapy (Review)". Oncology Letters 31, no. 1 (2026): 5. https://doi.org/10.3892/ol.2025.15358
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