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Role of post-translational modification of the Y box binding protein 1 in human cancers

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Genes & Diseases 2015年第3期2卷 240-246页

作者： Lakshmi Prabhu Antja-Voy Hartley Matthew Martin Fadumo Warsame Emily Sun Tao Lu Department of Pharmacology and Toxicology Indiana University School of Medicine635 Barnhill DriveIndianapolisIN 46202USA Department of Biochemistry and Molecular Biology Indiana University School of Medicine635 Barnhill DriveIndianapolisIN 46202USA Department of Medical and Molecular Genetics 975 West Walnut StreetMedical Research and Library BuildingIndianapolisIN 46202USA

Y box binding protein-1(YBX1)belongs to a DNA-and RNA-binding family of transcription factors,containing the highly conserved cold shock domain(CSD).YBX1 is involved in a number of cellular functions including transcription,translation,DNA damage repair etc.,and it is upregulated during times of environmental ***1 is localized in both the cytoplasm and the ***,its nuclear translocation is observed in a number of cancers and is associated with poor prognosis and disease ***,YBX1 expression is upregulated in a variety of cancers,pointing towards its role as a potential *** certain circumstances,YBX1 also promotes the expression of multidrug resistance 1(MDR1)gene,which is involved in the development of drug ***,it is critical to understand the mechanism of YBX1 regulation and its downstream effects on promoting cancer development.A number of recent studies have highlighted the mechanisms of YBX1 *** spectrometric analyses have reported several post-translational modifications that possibly play an important role in modulating YBX1 *** is the most widely occurring post-translational modification in *** vivo analyses of sites like S102 and more recently,S165 illustrate the relationship of post-translational regulation of YBX1 in promoting cell proliferation and tumor *** review provides a comprehensive and up-to-date account of post-translational modifications identified in *** knowledge is a key in allowing us to better understand the mechanism of YBX1 regulation,which will aid in development of novel therapeutic strategies to target YBX1 in many types of cancer in the future.

关键词： Cancer Cold shock domain Phosphorylation post-translational modification Y box binding protein 1

Applications of post-translational modifications of FoxO family proteins in biological functions

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Journal of Molecular Cell Biology 2011年第5期3卷 276-282页

作者： Ying Zhao Yachen Wang Wei-Guo Zhu Key Laboratory of Carcinogenesis and translational Research(Ministry of Education) Department of Biochemistry and Molecular BiologyPeking University Health Science CenterBeijing 100191China School of Oncology Peking University Health Science CenterBeijing 100191China

The functions of the FoxO family proteins,in particular their transcriptional activities,are modulated by post-translational modifi-cations(PTMs),including phosphorylation,acetylation,ubiquitination,methylation and *** PTMs occur in response to different cellular stresses,which in turn regulate the subcellular localization of FoxO family proteins,as well as their half-life,DNA binding,transcriptional activity and ability to interact with other cellular *** this review,we summarize the role of PTMs of FoxO family proteins in linking their biological and functional relevance with various diseases.

关键词： FoxO post-translational modification cancer

Protein post-translational modifications after spinal cord injury

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Neural Regeneration Research 2021年第10期16卷 1935-1943页

作者： Shuang Zhu Bing-Sheng Yang Si-Jing Li Ge Tong Jian-Ye Tan Guo-Feng Wu Lin Li Guo-Li Chen Qian Chen Li-Jun Lin Department of Joint and Orthopedics Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Department of Medical Ultrasonics Guangdong Province Key Laboratory of Hepatology ResearchThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Orthopedics Affiliated Hospital of Putian UniversityPutianFujian ProvinceChina Cell and Molecular Biology Laboratory Department of OrthopaedicsAlpert Medical School of Brown University/Rhode Island HospitalProvidenceRIUSA

Deficits in intrinsic neuronal capacities in the spinal cord,a lack of growth support,and suppression of axonal outgrowth by inhibitory molecules mean that spinal cord injury almost always has devastating *** such,one of the primary targets for the treatment of spinal cord injury is to develop strategies to antagonize extrinsic or intrinsic axonal growth-inhibitory factors or enhance the factors that support axonal *** these factors,a series of individual protein level disorders have been identified during the generation of axons following spinal cord ***,an increasing number of studies have indicated that post-translational modifications of these proteins have important implications for axonal *** researchers have discovered a variety of post-translational modifications after spinal cord injury,such as tyrosination,acetylation,and *** this review,we reviewed the post-translational modifications for axonal growth,functional recovery,and neuropathic pain after spinal cord injury,a better understanding of which may elucidate the dynamic change of spinal cord injury-related molecules and facilitate the development of a new therapeutic strategy for spinal cord injury.

关键词： extracellular matrix function impairment glial scar nerve regeneration neuropathic pain post-translational modification spinal cord injury therapeutic target

Diagnostic and Prognostic Value of Protein post-translational modifications in Hepatocellular Carcinoma

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Journal of Clinical and translational Hepatology 2023年第5期11卷 1192-1200页

作者： Jing Wang Fangfang Wang Ning Wang Mei-Yin Zhang Hui-Yun Wang Guo-Liang Huang Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdongChina China-America Cancer Research Institute Key Laboratory for Epigenetics of Dongguan CityGuangdong Medical UniversityDongguanGuangdongChina State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-Sen University Cancer CenterGuangzhouGuangdongChina

Hepatocellular carcinoma(HCC)is a common malignant tumor with high incidence and cancer mortality ***-translational modifications(PTMs)of proteins have a great impact on protein *** all proteins can undergo PTMs,including phosphorylation,acetylation,methylation,glycosylation,ubiquitination,and so *** studies have shown that PTMs are related to the occurrence and development of *** findings provide novel therapeutic targets for cancers,such as glypican-3 and *** clinical implications are also found in the studies of *** or prognostic value,and response to therapy have been *** HCC,it has been shown that glycosylated alpha-fetoprotein(AFP)has a higher detection rate for early liver cancer than conventional *** this review,we mainly focused on the diagnostic and prognostic value of PTM,in order to provide new insights into the clinical implication of PTM in HCC.

关键词： Diagnosis Hepatocellular carcinoma post-translational modification Prognosis

Mass Spectrometry Analysis of SARS-CoV-2 Nucleocapsid Protein Reveals Camouflaging Glycans and Unique post-translational modifications

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Infectious Microbes & Diseases 2021年第3期3卷 149-157页

作者： Zeyu Sun Xiaoqin Zheng Feiyang Ji Menghao Zhou Xiaoling Su Keyi Ren Lanjuan Li State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseaseThe First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina

The devastating coronavirus disease 2019(COVID-19)pandemic has prompted worldwide efforts to study structural biological traits of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and its viral *** to the Spike protein,which is the primary target for currently available vaccines or antibodies,knowledge about other virion structural components is *** high-resolution mass spectrometry,we report a comprehensive post-translational modification(PTM)analysis of nucleocapsid phosphoprotein(NCP),the most abundant structural component of the SARS-CoV-2 *** addition to phosphoryl groups,we show that the SARS-CoV-2 NCP is decorated with a variety of PTMs,including N-glycans and *** on newly identified PTMs,refined protein structural models of SARS-CoV-2 NCP were proposed and potential immune recognition epitopes of NCP were aligned with *** data can facilitate the design of novel vaccines or therapeutics targeting NCP,as valuable alternatives to the current vaccination and treatment paradigm that is under threat of the ever-mutating SARS-CoV-2 Spike protein.

关键词： glycosylation mass spectrometry nucleocapsid protein post-translational modification SARS-CoV-2

Systematic Analysis of post-translational modifications for Increased Longevity of Biotherapeutic Proteins

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Computational Molecular Bioscience 2024年第3期14卷 125-145页

作者： Justin Kim Karanveer Sadiora Thomas Jefferson High School for Science and Technology Alexandria VA USA

Protein-based therapeutics (PPTs) are drugs used to treat a variety of different conditions in the human body by alleviating enzymatic deficiencies, augmenting other proteins and drugs, modulating signal pathways, and more. However, many PPTs struggle from a short half-life due to degradation caused by irreversible protein aggregation in the bloodstream. Currently, the most researched strategies for improving the efficiency and longevity of PPTs are post-translational modifications (PTMs). The goal of our research was to determine which type of PTM increases longevity the most for each of three commonly-used therapeutic proteins by comparing the docking scores (DS) and binding free energies (BFE) from protein aggregation and reception simulations. DS and BFE values were used to create a quantitative index that outputs a relative number from −1 to 1 to show reduced performance, no change, or increased performance. Results showed that methylation was the most beneficial for insulin (p < 0.1) and human growth hormone (p < 0.0001), and both phosphorylation and methylation were somewhat optimal for erythropoietin (p < 0.1 and p < 0.0001, respectively). Acetylation consistently provided the worst benefits with the most negative indices, while methylation had the most positive indices throughout. However, PTM efficacy varied between PPTs, supporting previous studies regarding how each PTM can confer different benefits based on the unique structures of recipient proteins.

关键词： post-translational modification Protein-Based Therapeutics Therapeutic Half-Life Protein Aggregation Protein Reception

Functions and mechanisms of non-histone protein acetylation in plants^(∞)

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Journal of Integrative Plant Biology 2024年第10期66卷 2087-2101页

作者： Xia Jin Xiaoshuang Li Jaime A.Teixeira da Silva Xuncheng Liu Guangdong Provincial Key Laboratory of Applied Botany Key Laboratory of South China Agricultural Plant Molecular Analysis and Genetic ImprovementSouth China Botanical GardenChinese Academy of SciencesGuangzhou 510650China State Key Laboratory of Desert and Oasis Ecology Key Laboratory of Ecological Safety and Sustainable Development in Arid LandsXinjiang Institute of Ecology and GeographyChinese Academy of SciencesUrumqi 830000China Independent Researcher Miki-choKagawa-ken 761-0799Japan

Lysine acetylation, an evolutionarily conserved post-translational protein modification, is reversibly catalyzed by lysine acetyltransferases and lysine deacetylases. Lysine acetylation, which was first discovered on histones, mainly functions to configure the structure of chromatin and regulate gene transcriptional activity. Over the past decade, with advances in high-resolution mass spectrometry, a vast and growing number of non-histone proteins modified by acetylation in various plant species have been *** acetylation of non-histone proteins is widely involved in regulating biological processes in plants such as photosynthesis, energy metabolism, hormone signal transduction and stress responses. Moreover, in plants, lysine acetylation plays crucial roles in regulating enzyme activity,protein stability, protein interaction and subcellular localization. This review summarizes recent progress in our understanding of the biological functions and mechanisms of non-histone protein acetylation in plants. Research prospects in this field are also noted.

关键词： acetylomics lysine acetylation lysine deacetylation non-histone acetylation post-translational modification

Regulation of cytoskeleton-associated protein activities: Linking cellular signals to plant cytoskeletal function

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Journal of Integrative Plant Biology 2021年第1期63卷 241-250页

作者： Na Lian Xinwei Wang Yanping Jing Jinxing Lin Bejing Advanced Innovation Center for Tree Breeding by Molecular Design Bejing Forestry UniversityBeiing 100083China College of Biological Sciences and Biotechnology Beiing Forestry UniversityBeiing 100083China

The plant cytoskeleton undergoes dynamic remodeling in response to diverse developmental and environmental cues. Remodeling of the cytoskeleton coordinates growth in plant cells, including trafficking and exocytosis of membrane and wall components during cell expansion, and regulation of hypocotyl elongation in response to light. Cytoskeletal remodeling also has key functions in disease resistance and abiotic stress responses. Many stimuli result in altered activity of cytoskeleton-associatedproteins,microtubuleassociated proteins(MAPs) and actin-binding proteins(ABPs). MAPs and ABPs are the main players determining the spatiotemporally dynamic nature of the cytoskeleton, functioning in a sensory hub that decodes signals to modulate plant cytoskeletal behavior. Moreover, MAP and ABP activities and levels are precisely regulated during development and environmental responses, but our understanding of this process remains limited. In this review, we summarize the evidence linking multiple signaling pathways, MAP and ABP activities and levels, and cytoskeletal rearrangements in plant cells. We highlight advances in elucidating the multiple mechanisms that regulate MAP and ABP activities and levels, including calcium and calmodulin signaling, ROP GTPase activity, phospholipid signaling, and post-translational modifications.

关键词： calcium cytoskeleton-associated protein phospholipid plant cytoskeleton post-translational modification ROP

Acetylated-PPARγexpression is regulated by different P53 genotypes associated with the adipogenic differentiation of polyploid giant cancer cells with daughter cells

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Cancer Biology & Medicine 2023年第1期20卷 56-76页

作者： Kexin Zhang Xiaohui Yang Minying Zheng Yidi Ning Shiwu Zhang Tianjin Union Medical Center Tianjin 300122China Nankai University School of Medicine Nankai UniversityTianjin 300071China

Objective:Polyploid giant cancer cells(PGCCs)with daughter cells express epithelial–mesenchymal transition(EMT)-associated *** malignant tumor cells with EMT properties can transdifferentiate into mature tumor *** this study,we elucidated the potential for,and underlying mechanism of,adipogenic differentiation of PGCCs with daughter cells(PDCs).Methods:Cobalt chloride was used to induce PGCC formation in HEY(wild-type P53)and MDA-MB-231(mutant P53)cells;these cells were then cultured in adipogenic differentiation *** red O staining was used to confirm adipogenic differentiation,and the cell cycle was detected with flow *** expression of adipogenic differentiation-associated proteins and P300 histone acetyltransferase activity were compared before and after adipogenic *** xenograft models were used to confirm the adipogenic differentiation of ***:PDCs transdifferentiated into functional *** different cell cycle distributions were observed in PDCs after adipogenic *** expression levels of PPARγ,Ace-PPARγ,and Ace-P53 were higher in PDCs after adipogenic differentiation than in cells before adipogenic ***-PPARγand FABP4 expression increased in HEY cells and decreased in MDA-MB-231 PDCs after p53 knockdown.A485 treatment increased Ace-P53,Ace-PPARγ,and FABP4 expression in HEY PDCs by inhibiting SUMOylation of *** MDA-MB-231 PDCs,A485 treatment decreased Ace-P53,Ace-PPARγ,and FABP4 *** experiments also confirmed the adipogenic differentiation of ***:Acetylation of P53 and PPARγplays an important role in the adipogenic differentiation of PDCs.

关键词： PGCCs adipogenic differentiation PPARγ post-translational modification P53 genotype