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Article ; Online: Mutations of ribosomal protein genes induce overexpression of catalase in Saccharomyces cerevisiae.

Hsu, Ching-Hsiang / Liu, Ching-Yu / Lo, Kai-Yin

2024 Volume 24

Abstract: Ribosome assembly defects result in ribosomopathies, primarily caused by inadequate protein synthesis and induced oxidative stress. This study aimed to investigate the link between deleting one ribosomal protein gene (RPG) paralog and oxidative stress ... ...

Abstract	Ribosome assembly defects result in ribosomopathies, primarily caused by inadequate protein synthesis and induced oxidative stress. This study aimed to investigate the link between deleting one ribosomal protein gene (RPG) paralog and oxidative stress response. Our results indicated that RPG mutants exhibited higher oxidant sensitivity than the wild type (WT). The concentrations of H2O2 were increased in the RPG mutants. Catalase and superoxide dismutase (SOD) activities were generally higher at the stationary phase, with catalase showing particularly elevated activity in the RPG mutants. While both catalase genes, CTT1 and CTA1, consistently exhibited higher transcription in RPG mutants, Ctt1 primarily contributed to the increased catalase activity. Stress-response transcription factors Msn2, Msn4, and Hog1 played a role in regulating these processes. Previous studies have demonstrated that H2O2 can cleave 25S rRNA via the Fenton reaction, enhancing ribosomes' ability to translate mRNAs associated with oxidative stress-related genes. The cleavage of 25S rRNA was consistently more pronounced, and the translation efficiency of CTT1 and CTA1 mRNAs was altered in RPG mutants. Our results provide evidence that the mutations in RPGs increase H2O2 levels in vivo and elevate catalase expression through both transcriptional and translational controls.
MeSH term(s)	Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Catalase/genetics ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Ribosomal Proteins/genetics ; Ribosomal Proteins/metabolism ; Hydrogen Peroxide/pharmacology ; Oxidative Stress ; Superoxide Dismutase-1/metabolism ; Mutation
Chemical Substances	Catalase (EC 1.11.1.6) ; Saccharomyces cerevisiae Proteins ; Ribosomal Proteins ; Hydrogen Peroxide (BBX060AN9V) ; Superoxide Dismutase-1 (EC 1.15.1.1)
Language	English
Publishing date	2024-01-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2036775-2
ISSN	1567-1364 ; 1567-1356
ISSN (online)	1567-1364
ISSN	1567-1356
DOI	10.1093/femsyr/foae005
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Zs.A 5454: Show issues

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Article ; Online: Translation initiation factor eIF4G1 modulates assembly of the polypeptide exit tunnel region in yeast ribosome biogenesis.

Tseng, Yun-Ting / Sung, Yu-Cheng / Liu, Ching-Yu / Lo, Kai-Yin

Journal of cell science

2022 Volume 135, Issue 12

Abstract: eIF4G is an important eukaryotic translation initiation factor. In this study, eIF4G1, one of the eIF4G isoforms, was shown to directly participate in biogenesis of the large (60S) ribosomal subunit in Saccharomyces cerevisiae cells. Mutation of eIF4G1 ... ...

Abstract	eIF4G is an important eukaryotic translation initiation factor. In this study, eIF4G1, one of the eIF4G isoforms, was shown to directly participate in biogenesis of the large (60S) ribosomal subunit in Saccharomyces cerevisiae cells. Mutation of eIF4G1 decreased the amount 60S ribosomal subunits significantly. The C-terminal fragment of eIF4G1 could complement the function in 60S biogenesis. Analyses of its purified complex with mass spectrometry indicated that eIF4G1 associated with the pre-60S form directly. Strong genetic and direct protein-protein interactions were observed between eIF4G1 and Ssf1 protein. Upon deletion of eIF4G1, Ssf1, Rrp15, Rrp14 and Mak16 were abnormally retained on the pre-60S complex. This purturbed the loading of Arx1 and eL31 at the polypeptide exit tunnel (PET) site and the transition to a Nog2 complex. Our data indicate that eIF4G1 is important in facilitating PET maturation and 27S processing correctly. This article has an associated First Person interview with the first author of the paper.
MeSH term(s)	Eukaryotic Initiation Factor-4G/analysis ; Eukaryotic Initiation Factor-4G/genetics ; Eukaryotic Initiation Factor-4G/metabolism ; GTP Phosphohydrolases/metabolism ; Humans ; Models, Molecular ; Peptides/metabolism ; Ribosomal Proteins/genetics ; Ribosome Subunits, Large, Eukaryotic/metabolism ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/metabolism
Chemical Substances	Arx1 protein, S cerevisiae ; EIF4G1 protein, human ; Eukaryotic Initiation Factor-4G ; Peptides ; Ribosomal Proteins ; Saccharomyces cerevisiae Proteins ; GTP Phosphohydrolases (EC 3.6.1.-) ; NOG2 protein, S cerevisiae (EC 3.6.1.-)
Language	English
Publishing date	2022-06-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.259540
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Article ; Online: Functional Characterization and Structural Modeling of a Novel Glycine Oxidase from Variovorax paradoxus Iso1.

Lo, Kai-Yin / Tsai, Yi-Fang / Hsu, Chun-Hua / Lee, Chia-Yin

Applied and environmental microbiology

2022 Volume 88, Issue 23, Page(s) e0107722

Abstract: ... ...

Abstract	The
MeSH term(s)	Flavin-Adenine Dinucleotide/metabolism ; Sarcosine ; Escherichia coli/metabolism ; Amidohydrolases/genetics ; Amino Acids ; Substrate Specificity ; Alanine
Chemical Substances	glycine oxidase (EC 1.4.3.19) ; Flavin-Adenine Dinucleotide (146-14-5) ; Sarcosine (Z711V88R5F) ; Amidohydrolases (EC 3.5.-) ; Amino Acids ; Alanine (OF5P57N2ZX)
Language	English
Publishing date	2022-11-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	223011-2
ISSN	1098-5336 ; 0099-2240
ISSN (online)	1098-5336
ISSN	0099-2240
DOI	10.1128/aem.01077-22
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Article ; Online: Thallium(I) treatment induces nucleolar stress to stop protein synthesis and cell growth.

Chou, Yi-Ting / Lo, Kai-Yin

Scientific reports

2019 Volume 9, Issue 1, Page(s) 6905

Abstract: Thallium is considered as an emergent contaminant owing to its potential use in the superconductor alloys. The monovalent thallium, Tl(I), is highly toxic to the animals as it can affect numerous metabolic processes. Here we observed that Tl(I) decreased ...

Abstract	Thallium is considered as an emergent contaminant owing to its potential use in the superconductor alloys. The monovalent thallium, Tl(I), is highly toxic to the animals as it can affect numerous metabolic processes. Here we observed that Tl(I) decreased protein synthesis and phosphorylated eukaryotic initiation factor 2α. Although Tl(I) has been shown to interact with the sulfhydryl groups of proteins and cause the accumulation of reactive oxygen species, it did not activate endoplasmic reticulum stress. Notably, the level of 60S ribosomal subunit showed significant under-accumulation after the Tl(I) treatment. Given that Tl(I) shares similarities with potassium in terms of the ionic charge and atomic radius, we proposed that Tl(I) occupies certain K
MeSH term(s)	Apoptosis/drug effects ; Cell Cycle Checkpoints/drug effects ; Cell Nucleolus/drug effects ; Cell Nucleolus/metabolism ; Cell Proliferation/drug effects ; Dose-Response Relationship, Drug ; Eukaryotic Initiation Factor-2/biosynthesis ; Eukaryotic Initiation Factor-2/metabolism ; HEK293 Cells ; Humans ; Oxidative Stress/drug effects ; Phosphorylation/drug effects ; Ribosome Subunits, Large, Eukaryotic/drug effects ; Ribosome Subunits, Large, Eukaryotic/metabolism ; Thallium/toxicity ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Eukaryotic Initiation Factor-2 ; Tumor Suppressor Protein p53 ; Thallium (AD84R52XLF)
Language	English
Publishing date	2019-05-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-43413-1
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Article ; Online: Exploring the multifaceted impact of lanthanides on physiological pathways in human breast cancer cells.

Huang, Yi-Ming / Hsu, Tsu-Yu / Liu, Ching-Yu / Hsieh, Yu-Chen / Lai, Kuan-Yun / Yang, Ya-Wen / Lo, Kai-Yin

Toxicology

2024 Volume 502, Page(s) 153731

Abstract: Lanthanum (La) and cerium (Ce), rare earth elements with physical properties similar to calcium (Ca), are generally considered non-toxic when used appropriately. However, their ions possess anti-tumor capabilities. This investigation explores the ... ...

Abstract	Lanthanum (La) and cerium (Ce), rare earth elements with physical properties similar to calcium (Ca), are generally considered non-toxic when used appropriately. However, their ions possess anti-tumor capabilities. This investigation explores the potential applications and mechanisms of LaCl
MeSH term(s)	Humans ; Lanthanoid Series Elements ; Triple Negative Breast Neoplasms/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Calcium ; Cisplatin ; Lanthanum/toxicity ; Cell Line, Tumor
Chemical Substances	Lanthanoid Series Elements ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Calcium (SY7Q814VUP) ; Cisplatin (Q20Q21Q62J) ; Lanthanum (6I3K30563S)
Language	English
Publishing date	2024-01-20
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	184557-3
ISSN	1879-3185 ; 0300-483X
ISSN (online)	1879-3185
ISSN	0300-483X
DOI	10.1016/j.tox.2024.153731
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Zs.A 888: Show issues

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Article: Correction: Lin. et al. Effects of Substrate-Coating Materials on the Wound-Healing Process.

Lin, Jin-Young / Lo, Kai-Yin / Sun, Yung-Shin

Materials (Basel, Switzerland)

2020 Volume 13, Issue 1

Abstract: The authors wish to make the following correction to this paper [ ... ]. ...

Abstract	The authors wish to make the following correction to this paper [...].
Language	English
Publishing date	2020-01-06
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2487261-1
ISSN	1996-1944
ISSN	1996-1944
DOI	10.3390/ma13010248
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Article ; Online: High-dose copper activates p53-independent apoptosis through the induction of nucleolar stress in human cell lines.

Chen, Chieh-Hsin / Chou, Yi-Ting / Yang, Ya-Wen / Lo, Kai-Yin

Apoptosis : an international journal on programmed cell death

2021 Volume 26, Issue 11-12, Page(s) 612–627

Abstract: Copper is an essential micronutrient involved in many redox reactions in human cells. However, a high concentration of copper, intake from the environment or abnormal accumulation within cells because of genetic mutation, leads to cell toxicity. This is ... ...

Abstract	Copper is an essential micronutrient involved in many redox reactions in human cells. However, a high concentration of copper, intake from the environment or abnormal accumulation within cells because of genetic mutation, leads to cell toxicity. This is attributable to oxidative damage, altered gene expression, and functional impairment of the mitochondria. Copper stress also alters the morphology of the nucleolus, but the process has not been fully elucidated. In this study, cells were treated with copper sulfate at 3-9 ppm and examined if a high dose of copper would block ribosome biogenesis. With the incorrect distribution of nucleolar proteins nucleophosmin and fibrillarin to the nucleoplasm, ribosomal RNA (rRNA) processing was impaired; 34S rRNA from an abnormal A2 cut increased, and downstream pre-rRNAs decreased. The under-accumulation of 60S subunits was detected using sucrose gradients. From transcriptome analysis, ribosome synthesis-related genes were misregulated. Blockage in ribosome synthesis under copper-treatment induced nucleolar stress and triggered p53-independent apoptosis pathways. Thus, nucleolar stress is one cause of cell death under copper exposure.
MeSH term(s)	Apoptosis ; Cell Line ; Copper/toxicity ; Humans ; Nucleophosmin ; Tumor Suppressor Protein p53/genetics
Chemical Substances	Tumor Suppressor Protein p53 ; Nucleophosmin (117896-08-9) ; Copper (789U1901C5)
Language	English
Publishing date	2021-10-27
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1452360-7
ISSN	1573-675X ; 1360-8185
ISSN (online)	1573-675X
ISSN	1360-8185
DOI	10.1007/s10495-021-01692-y
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Zs.A 5178: Show issues

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Article ; Online: The dedicated chaperones of eL43, Puf6 and Loc1 can also bind RPL43 mRNA and regulate the production of this ribosomal protein.

Yueh, Le-Yun / Tseng, Yun-Ting / Chu, Chih-Yi / Lo, Kai-Yin

Journal of biochemistry

2021 Volume 171, Issue 1, Page(s) 85–96

Abstract: The level of ribosome biogenesis is highly associated with cell growth rate. Because many ribosomal proteins have extraribosomal functions, overexpression or insufficient supply of these proteins may impair cellular growth. Therefore, the supply of ... ...

Abstract	The level of ribosome biogenesis is highly associated with cell growth rate. Because many ribosomal proteins have extraribosomal functions, overexpression or insufficient supply of these proteins may impair cellular growth. Therefore, the supply of ribosomal proteins is tightly controlled in response to rRNA syntheses and environmental stimuli. In our previous study, two RNA-binding proteins, Puf6 and Loc1, were identified as dedicated chaperones of the ribosomal protein eL43, with which they associate to maintain its protein level and proper loading. In this study, we demonstrate that Puf6 and Loc1 interact with RPL43 mRNA. Notably, Puf6 and Loc1 usually function as a dimeric complex to bind other mRNAs; however, in this instance, the individual proteins, but not the complex form, can bind RPL43 mRNA. Thus, Puf6 or Loc1 could bind RPL43 mRNA in loc1Δ or puf6Δ, respectively. The binding of Puf6 or Loc1 caused negative effects for eL43 production: decreased RNA stability and translation of RPL43A/B mRNA. The present results suggest that these dedicated chaperones control the protein levels of eL43 from the standpoint of stability and through regulating its production.
MeSH term(s)	Nuclear Proteins/metabolism ; RNA, Messenger/genetics ; RNA-Binding Proteins/genetics ; Ribosomal Proteins/genetics ; Ribosomal Proteins/metabolism ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism
Chemical Substances	LOC1 protein, S cerevisiae ; Nuclear Proteins ; Puf6 protein, S cerevisiae ; RNA, Messenger ; RNA-Binding Proteins ; RPL43a protein, S cerevisiae ; Ribosomal Proteins ; Saccharomyces cerevisiae Proteins
Language	English
Publishing date	2021-11-15
Publishing country	England
Document type	Journal Article
ZDB-ID	218073-x
ISSN	1756-2651 ; 0021-924X
ISSN (online)	1756-2651
ISSN	0021-924X
DOI	10.1093/jb/mvab110
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Uc I Zs.202: Show issues

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Article ; Online: Gallium maltolate shows synergism with cisplatin and activates nucleolar stress and ferroptosis in human breast carcinoma cells.

Chen, Chieh-Hsin / Huang, Yi-Ming / Grillet, Louis / Hsieh, Yu-Chen / Yang, Ya-Wen / Lo, Kai-Yin

Cellular oncology (Dordrecht)

2023 Volume 46, Issue 4, Page(s) 1127–1142

Abstract: Purpose: Breast cancer is the most common cancer in women. Triple-negative breast cancer (TNBC) is an aggressive disease with poor outcomes. TNBC lacks effective targeted treatments, and the development of drug resistance limits the effectiveness of ... ...

Abstract	Purpose: Breast cancer is the most common cancer in women. Triple-negative breast cancer (TNBC) is an aggressive disease with poor outcomes. TNBC lacks effective targeted treatments, and the development of drug resistance limits the effectiveness of chemotherapy. It is crucial to identify new drugs that can enhance the efficacy of traditional chemotherapy to reduce drug resistance and side effects. Methods: TNBC cell lines, MDA-MB-231 and Hs 578T, and a normal cell line, MCF-10 A, were included in this study. The cells were treated with gallium maltolate (GaM), and their transcriptome was analyzed. Ferroptosis and nucleolar stress markers were detected by qPCR, western blotting, fluorescence microscopy, and flow cytometry. The impairment of ribosome synthesis was evaluated by northern blotting and sucrose gradients. Results: GaM triggered cell death via apoptosis and ferroptosis. In addition, GaM impaired translation and activated nucleolar stress. Cisplatin (DDP) is a chemotherapeutic agent for advanced breast cancer. While single treatment with GaM or DDP at low concentrations did not impact cell growth, co-administration enhanced cell death in TNBC but not in normal breast cells. The enhancement of ferroptosis and nucleolar stress could be observed in TNBC cell lines after co-treatment. Conclusions: These results suggest that GaM synergizes with cisplatin via activation of nucleolar stress and ferroptosis in human breast carcinoma cells. GaM is marginally toxic to normal cells but impairs the growth of TNBC cell lines. Thus, GaM has the potential to be used as a therapeutic agent against TNBC.
MeSH term(s)	Humans ; Female ; Cisplatin/pharmacology ; Cisplatin/therapeutic use ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Ferroptosis ; Triple Negative Breast Neoplasms/metabolism ; Cell Line, Tumor ; Apoptosis ; Cell Proliferation
Chemical Substances	Cisplatin (Q20Q21Q62J) ; Antineoplastic Agents ; gallium maltolate (17LEI49C2G)
Language	English
Publishing date	2023-04-17
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2595109-9
ISSN	2211-3436 ; 1875-8606 ; 2211-3428
ISSN (online)	2211-3436
ISSN	1875-8606 ; 2211-3428
DOI	10.1007/s13402-023-00804-x
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Zs.A 6908: Show issues

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Article: Effects of Substrate-Coating Materials on the Wound-Healing Process.

Lin, Jin-Young / Lo, Kai-Yin / Sun, Yung-Shin

Materials (Basel, Switzerland)

2019 Volume 12, Issue 17

Abstract: The wound-healing assay is commonly and widely used for investigating collective cell migration under various physical and chemical stimuli. Substrate-coating materials are shown to affect the wound-healing process in a cell-type dependent manner. ... ...

Abstract	The wound-healing assay is commonly and widely used for investigating collective cell migration under various physical and chemical stimuli. Substrate-coating materials are shown to affect the wound-healing process in a cell-type dependent manner. However, experiment-to-experiment variations make it difficult to compare results from different assays. In this paper, a modified barrier wound-healing assay was reported for studying the wound-healing process on different substrates in one single petri dish. In short, half of a dish was covered with the tape, and coating materials, poly-l-lysine and gelatin, were applied to the surface. After peeling off the tape, half of the surface was coated with the desired material. Then a customized barrier was placed inside the dish to create the wound. The results indicated that surface coating did not affect cell proliferation/viability, and the wound-healing rate increased in coated surfaces compared to uncoated ones. The present study provides a platform for further understanding the mechanisms of substrate coating-dependent wound-healing processes.
Language	English
Publishing date	2019-08-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2487261-1
ISSN	1996-1944
ISSN	1996-1944
DOI	10.3390/ma12172775
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