Phosphodegrons in Health and Disease: From Cellular Homeostasis to Therapeutic Potential

Phosphodegrons are critical motifs that play a pivotal role in the regulation of protein stability and function via phosphorylation-dependent signaling pathways. These motifs serve as recognition elements for ubiquitin ligases, facilitating the targeted degradation of proteins. By modulating key cel...

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Main Authors: Tadashi Nakagawa, Makiko Nakagawa
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Kinases and Phosphatases
Subjects:
Online Access:https://www.mdpi.com/2813-3757/3/1/3
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author Tadashi Nakagawa
Makiko Nakagawa
author_facet Tadashi Nakagawa
Makiko Nakagawa
author_sort Tadashi Nakagawa
collection DOAJ
description Phosphodegrons are critical motifs that play a pivotal role in the regulation of protein stability and function via phosphorylation-dependent signaling pathways. These motifs serve as recognition elements for ubiquitin ligases, facilitating the targeted degradation of proteins. By modulating key cellular processes such as cell cycle progression, DNA repair, and apoptosis, phosphodegrons are essential for maintaining cellular homeostasis. Dysregulation of phosphodegrons has been implicated in a wide range of diseases, including cancer and neurodegenerative disorders, highlighting their potential as therapeutic targets. This review provides an overview of phosphodegron functions along with their biological significance in health and disease. Additionally, we discuss current methodologies for studying phosphodegrons and explore emerging trends in their identification and therapeutic targeting. By synthesizing recent advances in the field, this article aims to offer insights into the future directions and challenges in phosphodegron research, ultimately underscoring their importance in cellular regulation and disease pathology.
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spelling doaj-art-9364c22aa7484cb3917b5f0c9e03c0da2025-08-20T01:49:00ZengMDPI AGKinases and Phosphatases2813-37572025-02-0131310.3390/kinasesphosphatases3010003Phosphodegrons in Health and Disease: From Cellular Homeostasis to Therapeutic PotentialTadashi Nakagawa0Makiko Nakagawa1Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Sanyo-Onoda 756-0084, JapanInstitute of Gene Research, Yamaguchi University Science Research Center, Yamaguchi 755-8505, JapanPhosphodegrons are critical motifs that play a pivotal role in the regulation of protein stability and function via phosphorylation-dependent signaling pathways. These motifs serve as recognition elements for ubiquitin ligases, facilitating the targeted degradation of proteins. By modulating key cellular processes such as cell cycle progression, DNA repair, and apoptosis, phosphodegrons are essential for maintaining cellular homeostasis. Dysregulation of phosphodegrons has been implicated in a wide range of diseases, including cancer and neurodegenerative disorders, highlighting their potential as therapeutic targets. This review provides an overview of phosphodegron functions along with their biological significance in health and disease. Additionally, we discuss current methodologies for studying phosphodegrons and explore emerging trends in their identification and therapeutic targeting. By synthesizing recent advances in the field, this article aims to offer insights into the future directions and challenges in phosphodegron research, ultimately underscoring their importance in cellular regulation and disease pathology.https://www.mdpi.com/2813-3757/3/1/3phosphodegronsubiquitin–proteasome system (UPS)ubiquitin ligasesprotein degradationprotein phosphorylationdisease pathology
spellingShingle Tadashi Nakagawa
Makiko Nakagawa
Phosphodegrons in Health and Disease: From Cellular Homeostasis to Therapeutic Potential
Kinases and Phosphatases
phosphodegrons
ubiquitin–proteasome system (UPS)
ubiquitin ligases
protein degradation
protein phosphorylation
disease pathology
title Phosphodegrons in Health and Disease: From Cellular Homeostasis to Therapeutic Potential
title_full Phosphodegrons in Health and Disease: From Cellular Homeostasis to Therapeutic Potential
title_fullStr Phosphodegrons in Health and Disease: From Cellular Homeostasis to Therapeutic Potential
title_full_unstemmed Phosphodegrons in Health and Disease: From Cellular Homeostasis to Therapeutic Potential
title_short Phosphodegrons in Health and Disease: From Cellular Homeostasis to Therapeutic Potential
title_sort phosphodegrons in health and disease from cellular homeostasis to therapeutic potential
topic phosphodegrons
ubiquitin–proteasome system (UPS)
ubiquitin ligases
protein degradation
protein phosphorylation
disease pathology
url https://www.mdpi.com/2813-3757/3/1/3
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