A Perspective on Therapeutic Targeting Against Ubiquitin Ligases to Stabilize Tumor Suppressor Proteins

Ishaar P. Ganesan; Hiroaki Kiyokawa

doi:10.3390/cancers17040626

A Perspective on Therapeutic Targeting Against Ubiquitin Ligases to Stabilize Tumor Suppressor Proteins

Ishaar P. Ganesan, Hiroaki Kiyokawa^*

^*Corresponding author for this work

Pharmacology

Research output: Contribution to journal › Review article › peer-review

Abstract

During cancer development, tumor suppressor proteins undergo inactivation due to genetic, epigenetic, or post-translational alterations. While the concept of reactivating tumor suppressor proteins has been appreciated as a potential anti-cancer therapeutic strategy for decades, progress in developing therapies that target tumor suppressor proteins has lagged behind the successful development of therapies targeting oncoproteins such as protein kinases. Here, we review the status and potential of therapeutic targeting against ubiquitin ligases as a promising approach to stabilize and reactivate tumor suppressor proteins.

Original language	English (US)
Article number	626
Journal	Cancers
Volume	17
Issue number	4
DOIs	https://doi.org/10.3390/cancers17040626
State	Published - Feb 2025

Funding

This study has been supported in part by the NIH R01GM104498 grant, the Director\u2019s Fund from the Chicago Biomedical Consortium, and the Northwestern NewCures program (all to H.K.).

Keywords

CDK inhibitor
FBXW7
MDM2
PML
PTEN
UBE3A
drug development
p53
tumor suppressor
ubiquitin

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers17040626

Cite this

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title = "A Perspective on Therapeutic Targeting Against Ubiquitin Ligases to Stabilize Tumor Suppressor Proteins",

abstract = "During cancer development, tumor suppressor proteins undergo inactivation due to genetic, epigenetic, or post-translational alterations. While the concept of reactivating tumor suppressor proteins has been appreciated as a potential anti-cancer therapeutic strategy for decades, progress in developing therapies that target tumor suppressor proteins has lagged behind the successful development of therapies targeting oncoproteins such as protein kinases. Here, we review the status and potential of therapeutic targeting against ubiquitin ligases as a promising approach to stabilize and reactivate tumor suppressor proteins.",

keywords = "CDK inhibitor, FBXW7, MDM2, PML, PTEN, UBE3A, drug development, p53, tumor suppressor, ubiquitin",

author = "Ganesan, {Ishaar P.} and Hiroaki Kiyokawa",

note = "Publisher Copyright: {\textcopyright} 2025 by the authors.",

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volume = "17",

journal = "Cancers",

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T1 - A Perspective on Therapeutic Targeting Against Ubiquitin Ligases to Stabilize Tumor Suppressor Proteins

AU - Ganesan, Ishaar P.

AU - Kiyokawa, Hiroaki

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Y1 - 2025/2

N2 - During cancer development, tumor suppressor proteins undergo inactivation due to genetic, epigenetic, or post-translational alterations. While the concept of reactivating tumor suppressor proteins has been appreciated as a potential anti-cancer therapeutic strategy for decades, progress in developing therapies that target tumor suppressor proteins has lagged behind the successful development of therapies targeting oncoproteins such as protein kinases. Here, we review the status and potential of therapeutic targeting against ubiquitin ligases as a promising approach to stabilize and reactivate tumor suppressor proteins.

AB - During cancer development, tumor suppressor proteins undergo inactivation due to genetic, epigenetic, or post-translational alterations. While the concept of reactivating tumor suppressor proteins has been appreciated as a potential anti-cancer therapeutic strategy for decades, progress in developing therapies that target tumor suppressor proteins has lagged behind the successful development of therapies targeting oncoproteins such as protein kinases. Here, we review the status and potential of therapeutic targeting against ubiquitin ligases as a promising approach to stabilize and reactivate tumor suppressor proteins.

KW - CDK inhibitor

KW - FBXW7

KW - MDM2

KW - PML

KW - PTEN

KW - UBE3A

KW - drug development

KW - p53

KW - tumor suppressor

KW - ubiquitin

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U2 - 10.3390/cancers17040626

DO - 10.3390/cancers17040626

M3 - Review article

C2 - 40002221

AN - SCOPUS:85218452498

SN - 2072-6694

VL - 17

JO - Cancers

JF - Cancers

IS - 4

M1 - 626

ER -

A Perspective on Therapeutic Targeting Against Ubiquitin Ligases to Stabilize Tumor Suppressor Proteins

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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