S-glutathionylation of Hsp90 enhances its degradation and correlates with favorable prognosis of breast cancer

Shih, Yu-Yin; Lin, Hong-Shiang; Jan, Hau-Ming; Chen, Yu‐Ju; Ong, Lih-Lih; Yu, Alice L.; Lin, Chun‐Hung

doi:10.1016/j.redox.2022.102501

Cited by 6 publications

(6 citation statements)

References 34 publications

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“…The protein stability assay was according to the previous reports 20–22 . Briefly, the DMSO‐treated NEP cells (Day 7) and RE‐treated NEP cells (Day 7) were treated with an inhibitor of protein synthesis, cycloheximide (CHX, 100 μg/mL; Sigma, USA).…”

Section: Methodsmentioning

confidence: 99%

“…The protein stability assay was according to the previous reports. 20 , 21 , 22 Briefly, the DMSO‐treated NEP cells (Day 7) and RE‐treated NEP cells (Day 7) were treated with an inhibitor of protein synthesis, cycloheximide (CHX, 100 μg/mL; Sigma, USA). The cells were obtained at indicated times for analysing the protein stability of NR2F1 by Western blotting.…”

Section: Methodsmentioning

confidence: 99%

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NAT10‐mediated ac⁴C modification promotes ectoderm differentiation of human embryonic stem cells via acetylating NR2F1 mRNA

Ge,

Wang,

2023

Cell Proliferation

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Cell fate determination in mammalian development is complex and precisely controlled and accumulating evidence indicates that epigenetic mechanisms are crucially involved. N4‐acetylcytidine (ac4C) is a recently identified modification of messenger RNA (mRNA); however, its functions are still elusive in mammalian. Here, we show that N‐acetyltransferase 10 (NAT10)‐mediated ac4C modification promotes ectoderm differentiation of human embryonic stem cells (hESCs) by acetylating nuclear receptor subfamily 2 group F member 1 (NR2F1) mRNA to enhance translation efficiency (TE). Acetylated RNA immunoprecipitation sequencing (acRIP‐seq) revealed that levels of ac4C modification were higher in ectodermal neuroepithelial progenitor (NEP) cells than in hESCs or mesoendoderm cells. In addition, integrated analysis of acRIP‐seq and ribosome profiling sequencing revealed that NAT10 catalysed ac4C modification to improve TE in NEP cells. RIP‐qRT‐PCR analysis identified an interaction between NAT10 and NR2F1 mRNA in NEP cells and NR2F1 accelerated the nucleus‐to‐cytoplasm translocation of yes‐associated protein 1, which contributed to ectodermal differentiation of hESCs. Collectively, these findings point out the novel regulatory role of ac4C modification in the early ectodermal differentiation of hESCs and will provide a new strategy for the treatment of neuroectodermal defects diseases.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

NAT10‐mediated ac⁴C modification promotes ectoderm differentiation of human embryonic stem cells via acetylating NR2F1 mRNA

Ge,

Wang,

2023

Cell Proliferation

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“…S‐glutathionylation of Hsp90 results in inactivation of ATPase. 1340 S‐glutathionylation of C/EBPβ stabilizes the protein and increases its levels, promoting 3T3l1 cell differentiation. 1341 Additionally, S‐glutathionylation plays a role in regulating apoptosis.…”

Section: Redox Modificationsmentioning

confidence: 99%

“…Hsp90 is a widely distributed molecular chaperone that interacts with a variety of proteins and regulates a variety of cellular processes. S‐glutathionylation of Hsp90 results in inactivation of ATPase 1340 . S‐glutathionylation of C/EBPβ stabilizes the protein and increases its levels, promoting 3T3l1 cell differentiation 1341 .…”

Section: Redox Modificationsmentioning

confidence: 99%

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Zhong

Xiao

Xie

et al. 2023

MedComm

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Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on the backbones or amino acid side chains of proteins and expand the diversity of proteins, which provides the basis for the emergence of organismal complexity. To date, more than 650 types of protein modifications, such as the most well‐known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short‐chain and long‐chain acylation modifications, redox modifications, and irreversible modifications, have been described, and the inventory is still increasing. By changing the protein conformation, localization, activity, stability, charges, and interactions with other biomolecules, PTMs ultimately alter the phenotypes and biological processes of cells. The homeostasis of protein modifications is important to human health. Abnormal PTMs may cause changes in protein properties and loss of protein functions, which are closely related to the occurrence and development of various diseases. In this review, we systematically introduce the characteristics, regulatory mechanisms, and functions of various PTMs in health and diseases. In addition, the therapeutic prospects in various diseases by targeting PTMs and associated regulatory enzymes are also summarized. This work will deepen the understanding of protein modifications in health and diseases and promote the discovery of diagnostic and prognostic markers and drug targets for diseases.

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“…The USP2 inhibitor ML364 inhibits tumor growth and enhances the sensitivity to Adriamycin ( 102 ). In addition, the molecular chaperone function of heat shock protein 90 (HSP90) serves a critical role in maintaining the stability of various intracellular proteins and is closely associated with the development of several tumors ( 119 , 120 ). Clinical trials have demonstrated the anticancer effects of multiple HSP90 inhibitors, both as monotherapy and combination therapy with ErbB2-targeting agents ( 121 , 122 ).…”

Section: Targeting Usp2 For Cancer Therapymentioning

confidence: 99%

Targeting the deubiquitinase USP2 for malignant tumor therapy (Review)

Zhang,

Guo,

Zhang

et al. 2023

Oncol Rep

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The ubiquitin-proteasome system is a major degradation pathway for >80% of proteins in vivo. Deubiquitylases, which remove ubiquitinated tags to stabilize substrate proteins, are important components involved in regulating the degradation of ubiquitinated proteins. In addition, they serve multiple roles in tumor development by participating in physiological processes such as protein metabolism, cell cycle regulation, DNA damage repair and gene transcription. The present review systematically summarized the role of ubiquitin-specific protease 2 (USP2) in malignant tumors and the specific molecular mechanisms underlying the involvement of USP2 in tumor-associated pathways. USP2 reverses ubiquitin-mediated degradation of proteins and is involved in aberrant proliferation, migration, invasion, apoptosis and drug resistance of tumors. Additionally, the present review summarized studies reporting on the use of USP2 as a therapeutic target for malignancies such as breast, liver, ovarian, colorectal, bladder and prostate cancers and glioblastoma and highlights the current status of pharmacological research on USP2. The clinical significance of USP2 as a therapeutic target for malignant tumors warrants further investigation. Contents 1. Introduction 2. Role of USP2 in the biological behavior of malignant tumors 3. Targeting USP2 for cancer therapy 4. Pharmacological studies of USP2 5. Concluding remarks and potential future directions

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S-glutathionylation of Hsp90 enhances its degradation and correlates with favorable prognosis of breast cancer

Cited by 6 publications

References 34 publications

NAT10‐mediated ac⁴C modification promotes ectoderm differentiation of human embryonic stem cells via acetylating NR2F1 mRNA

NAT10‐mediated ac⁴C modification promotes ectoderm differentiation of human embryonic stem cells via acetylating NR2F1 mRNA

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Targeting the deubiquitinase USP2 for malignant tumor therapy (Review)

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S-glutathionylation of Hsp90 enhances its degradation and correlates with favorable prognosis of breast cancer

Cited by 6 publications

References 34 publications

NAT10‐mediated ac4C modification promotes ectoderm differentiation of human embryonic stem cells via acetylating NR2F1 mRNA

NAT10‐mediated ac4C modification promotes ectoderm differentiation of human embryonic stem cells via acetylating NR2F1 mRNA

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Targeting the deubiquitinase USP2 for malignant tumor therapy (Review)

Contact Info

Product

Resources

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NAT10‐mediated ac⁴C modification promotes ectoderm differentiation of human embryonic stem cells via acetylating NR2F1 mRNA

NAT10‐mediated ac⁴C modification promotes ectoderm differentiation of human embryonic stem cells via acetylating NR2F1 mRNA