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Damage Mechanism of CK2 and IKAROS in Philadelphia Like Acute Lymphoblastic Leukemia

Journal of Biosciences and Medicines 2024年第4期12卷 49-59页

作者： Ignacio Vélez-Rodríguez Victoria Carranza-Aranda Facultad Mexicana de Medicina Universidad La Salle Tlalpan M&#233xico Hospital General de Mé xico Cuauht&#233moc M&#233xico

Acute lymphoblastic leukemia (ALL) is characterized by immature and poorly differentiated B lymphocytes in large numbers in the blood. B cells are distinct from the cell types involved in their development (common lymphoid progenitor cells, pro-B cells, pre-B cells, and mature cells). The process of B cell maturation depends on precise communication within the cell: signals activate specific genes that are essential for proper development. Errors in this intricate signaling network can lead to issues with B cell function and contribute to disease. B-lineage acute lymphoid leukemias, malignancies of precursor-stage B lymphoid cells inhibit lymphoid differentiation, leading to abnormal cell proliferation and survival. The process of developing leukemia (leukemogenesis) can be triggered by an overproduction of both hematopoietic stem cells (the cells that form all blood cells) and the immature versions of white blood cells called lymphoblasts. Acute lymphoblastic leukemia (ALL) with the presence of the Philadelphia chromosome (ALL Ph) is classified as a high-risk manifestation of the disease, this chromosome is the product of the reciprocal translocation, whose product is a BCR-ABL fusion protein. It is a highly active tyrosine kinase that can transform hematopoietic cells into cytokine-independent. Hyperphosphorylation cascades inhibit the differentiating function of IKZF1 as a tumor suppressor gene which leads to an abnormal proliferation of B cells due to the presence of the Philadelphia chromosome;it inhibits the differentiating process, leukemogenesis involving immature B cells in the bloodstream can result from the uncontrolled growth and division of hematopoietic stem cells and immature lymphoblasts (the precursors to B cells).

关键词： Acute Lymphoblastic Leukemia IKAROS dephosphorylation Philadelphia Chromosome CK2

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Ca^(2+)-dependent TaCCD1 cooperates with TaSAUR215 to enhance plasma membrane H^(+)-ATPase activity and alkali stress tolerance by inhibiting PP2C-mediated dephosphorylation of TaHA2 in wheat

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Molecular Plant 2023年第3期16卷 571-587页

作者： Minghan Cui Yanping Li Jianhang Li Fengxiang Yin Xiangyu Chen Lumin Qin Lin Wei Guangmin Xia Shuwei Liu Key Laboratory of Plant Development and Environmental Adaptation Biology Ministry of EducationSchool of Life ScienceShandong UniversityQingdao 266237China

Alkali stress is a major constraint for crop production in many regions of saline-alkali land.However,little is known about the mechanisms through which wheat responds to alkali stress.In this study,we identified a calcium ion-binding protein from wheat,TaCCD1,which is critical for regulating the plasma membrane(PM)H^(+)-ATPase-mediated alkali stress response.PM H+-ATPase activity is closely related to alkali tolerance in the wheat variety Shanrong 4(SR4).We found that two D-clade type 2C protein phosphatases,TaPP2C.D1 and TaPP2C.D8(TaPP2C.D1/8),negatively modulate alkali stress tolerance by dephosphorylating the penultimate threonine residue(Thr926)of TaHA2 and thereby inhibiting PM H+-ATPase activity.Alkali stress induces the expression of TaCCD1 in SR4,and TaCCD1 interacts with TaSAUR215,an early auxin-responsive protein.These responses are both dependent on calcium signaling triggered by alkali stress.TaCCD1 enhances the inhibitory effect of TaSAUR215 on TaPP2C.D1/8 activity,thereby promoting the activity of the PM H^(+)-ATPase TaHA2 and alkali stress tolerance in wheat.Functional and genetic analyses verified the effects of these genes in response to alkali stress,indicating that TaPP2C.D1/8 function downstream of TaSAUR215 and TaCCD1.Collectively,this study uncovers a new signaling pathway that regulates wheat responses to alkali stress,in which Ca^(2+)-dependent TaCCD1 cooperates with TaSAUR215 to enhance PM H+-ATPase activity and alkali stress tolerance by inhibiting TaPP2C.D1/8-mediated dephosphorylation of PM H+-ATPase TaHA2 in wheat.

关键词： Triticum aestivum alkali stress resistance calcium-binding protein small auxin-up RNA plasma membrane H+-ATPase dephosphorylation

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C60 Fullerenes Suppress Reactive Oxygen Species Toxicity Damage in Boar Sperm

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Nano-Micro Letters 2019年第4期11卷 817-833页

作者： Xinhong Li Lirui Wang Huan Liu Jieli Fu Linqing Zhen Yuhua Li Yaozhong Zhang Yafei Zhang Shanghai Key Laboratory of Veterinary Biotechnology School of Agriculture and BiologyShanghai Jiao Tong UniversityShanghai 200240People’s Republic of China Institute of Nano Biomedicine and Engineering Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment InstrumentDepartment of Instrument Science and EngineeringSchool of Electronic Information and Electrical EngineeringShanghai Jiao Tong UniversityShanghai 200240People’s Republic of China Department of Electrical and Computer Engineering Michigan State UniversityEast LansingUSA Key Laboratory of Thin Film and Microfabrication(Ministry of Education) Department of Micro/Nano ElectronicsSchool of ElectronicsInformation and Electrical EngineeringShanghai Jiao Tong UniversityShanghai 200240People’s Republic of China

We report the carboxylated C60 improved the survival and quality of boar sperm during liquid storage at 4°C and thus propose the use of carboxylated C60 as a novel antioxidant semen extender supplement.Our results demonstrated that the sperm treated with 2μg mL?1 carboxylated C60 had higher motility than the control group(58.6%and 35.4%,respectively;P?0.05).Moreover,after incubation with carboxylated C60 for 10 days,acrosome integrity and mitochondrial activity of sperm increased by 18.1%and 34%,respectively,compared with that in the control group.Similarly,the antioxidation abilities and adenosine triphosphate levels in boar sperm treated with carboxylated C60 significantly increased(P?0.05)compared with those in the control group.The presence of carboxylated C60 in semen extender increases sperm motility probably by suppressing reactive oxygen species(ROS)toxicity damage.Interestingly,carboxylated C60 could protect boar sperm from oxidative stress and energy deficiency by inhibiting the ROS-induced protein dephosphorylation via the cAMP-PKA signaling pathway.In addition,the safety of carboxylated C60 as an alternative antioxidant was also comprehensively evaluated by assessing the mean litter size and number of live offspring in the carboxylated C60 treatment group.Our findings confirm carboxylated C60 as a novel antioxidant agent and suggest its use as a semen extender supplement for assisted reproductive technology in domestic animals.

关键词： Carboxylated C60 Semen preservation Oxidative stress Motility Protein dephosphorylation

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Nucleoprotein phosphorylation site(Y385)mutation confers temperature sensitivity to influenza A virus due to impaired nucleoprotein oligomerization at a lower temperature

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Science China(Life Sciences) 2021年第4期64卷 633-643页

作者： Weinan Zheng Liang Cui Minghui Li Yun Li Wenhui Fan Limin Yang Jing Li Lei Sun Wenjun Liu CAS Key Laboralory of Pathogenic Microbiology and Immumology Institute of MicrobiologyChinese Academy of SciencesBejing 100101China University of Chinese Academy of Sciences Bejing 100101China State Key Laboratory for Conservation and Urilization of Subtropical Agro-Bioresourses&Laboratory of Animal Infectious Diseases College of Animal Sciences and Veterinary MedicineGuangxi UniversitNanning 530004China Instinute of Microbiology Center for Biosafety Mega-ScienceChinese Academy of SciencesBeijing 100101China

Mutations in viral proteins can lead to the cold adaption of influenza A virus and the cold-adapted virus is an important vaccination instrument.Here,we identify a novel strain of influenza A virus with cold sensitivity conferred by a mutation at a phosphorylation site within the nucleoprotein(NP).The highly conserved tyrosine 385 residue(Y385)of NP was identified as a phosphorylation site by mass spectrometry.The constructive NP phosphorylation mimicked by Y385 E mutation was fatal for virus replication,while the continuous Y385 dephosphorylation mimicked by Y385 F mutation had little impact on virus replication in vitro.Notably,the Y385 F virus showed much lower replicative capacity in turbinates of mice compared with the wild type virus.Moreover,the replication of Y385 F virus was significantly reduced in both A549 and MDCK cells grown at 33℃,when compared to that at 37℃.These results indicated that the Y385 F mutation led to cold sensitivity of virus.We further found that the cold sensitivity of Y385 F virus could be attributed to diminished NP oligomerization rather than any changes in intracellular localization.Taken together,these findings suggest that the phosphorylation of NP may be a critical factor that regulates the temperature sensitivity of influenza A virus.

关键词： influenza A virus nucleoprotein phosphorylation dephosphorylation temperature sensitivity

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Src Is Dephosphorylated at Tyrosine 530 in Human Colon Carcinomas

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Chinese Journal of Cancer Research 2011年第3期23卷 229-231页

作者： Jeffrey D Bjorge Donald J Fujita Department of Biochemistry and Molecular Biology and Southern Alberta Cancer Research InstituteUniversity of Calgary

Objective：Src is a protein tyrosine kinase that plays important roles in cancer development,and Src kinase activity has been found to be elevated in several types of cancers.However,the cause of the elevation of Src kinase activity in the majority of human colon carcinomas is still largely unknown.We aim at finding the cause of elevated Src kinase activity in human colon carcinomas.Methods：We employed normal colon epithelial FHC cells and examined Src activation in human colon carcinoma specimens from 8 patients.Protein expression levels were determined by Western blotting,and the activity of Src kinase by kinase assay.Results：Actin levels were different between tumor and normal tissues,demonstrating the complexities and inhomogeneities of the tissue samples.Src kinase activities were increased in the majority of the colon carcinomas as compared with normal colon epithelial cells （range 13-29）.Src protein levels were reduced in the colon carcinomas.Src Y530 phosphorylation levels were reduced to a higher extent than protein levels in the carcinomas.Conclusion：The results suggest that Src specific activities were highly increased in human colon carcinomas;phosphorylation at Src Y530 was reduced,contributing to the highly elevated Src specific activity and Src kinase activity.

关键词： Src Kinase activation dephosphorylation Colon carcinoma

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Assembly and structure of protein phosphatase 2A

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Science China(Life Sciences) 2009年第2期52卷 135-146页

作者： SHI Yi Gong Center for Structural Biology, Department of Biological Sciences and Biotechnology, and School of Medicine, Tsinghua University, Beijing 100084, China Center for Structural Biology Department of Biological Sciences and Biotechnology and School of Medicine Tsinghua University Beijing China

Protein phosphatase 2A (PP2A) represents a conserved family of important protein serine/threonine phosphatases in species ranging from yeast to human. The PP2A core enzyme comprises a scaffold subunit and a catalytic subunit. The heterotrimeric PP2A holoenzyme consists of the core enzyme and a variable regulatory subunit. The catalytic subunit of PP2A is subject to reversible methylation, medi-ated by two conserved enzymes. Both the PP2A core and holoenzymes are regulated through interac-tion with a large number of cellular cofactors. Recent biochemical and structural investigation reveals critical insights into the assembly and function of the PP2A core enzyme as well as two families of holoenzyme. This review focuses on the molecular mechanisms revealed by these latest advances.

关键词： protein phosphorylation dephosphorylation PP2A structure mechanism

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Molecular cloning and differential expression patterns of the regulatory subunit B' gene of PP2A in goldfish,Carassius auratus

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Science China(Life Sciences) 2009年第8期52卷 724-732页

作者： LI David WanCheng Key Laboratory of Protein Chemistry & Developmental Biology of Education Ministry of China College of Life SciencesHunan Normal University Department of Biochemistry and Molecular Biology College of MedicineUniversity of Nebraska Medical Center Department of Ophthalmology and Visual Sciences College of MedicineUniversity of Nebraska Medical Center

It is well established that the protein serine/threonine phosphatase 2A(PP2A) plays very important roles in many different cellular processes,including cell proliferation and differentiation,gene expression,neurotransmission,apoptosis,and aging.PP2A consists of three heterogenic subunits:the scaffold subunit A,the catalytic subunit C,and the regulatory subunit B.While both the scaffold and the catalytic subunits contain only two forms,at least four families of the regulatory subunits,B,B',B'',and B''' have been identified.These regulatory subunits from different families are encoded by different genes and bear other functions besides directing the specificity of PP2A.To study the functions of the regulatory subunits of PP2A in lower vertebrates,we have cloned the full-length cDNA sequence of the gene encoding the regulatory subunit B'δ of PP2A from gold fish,Carassius auratus using 3'-RACE and 5'-RACE cloning strategies.Our results revealed that the full-length B'δ cDNA contains 2415 bp and encodes a protein of 555 amino acids.The B'δ protein displays a very high level of sequence identity with the B'δ regulatory subunit from other species of vertebrates.Regarding its expression pattern,RT-PCR revealed that the highest level of mRNA was detected in brain,a less level detected in liver,spermary,ovary,kidney and gill,and the lowest level detected in the fin.During different developmental stages of gold fish,the highest level of mRNA expression was detected at the stages of two-cell,multiple-cell,blastula and gastrula,and a decreased level of B'δ mRNA was detected in other developmental stages.At the protein level,the highest expression level of B'δ protein was found in spermary,ovary,brain and heart,a less amount found in liver and the lowest level detected in kidney,gill and fin.Developmentally,B'δ protein was strongly expressed at the stages of two-cell,multiple-cell,blastula,gastrula,neurula,and optic vesicle,and then decreased at the stages of brain differentiation and eye pigmentation.These results suggest tha

关键词： PP2A Protein dephosphorylation PP2A-B’δ regulatory subunit.

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Active zone stability:insights from fly neuromuscular junction

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Neural Regeneration Research 2015年第5期10卷 677-678页

作者： Xiaolin Tian Chunlai Wu Neuroscience Center of Excellence Department of Cell Biology and AnatomySchool of MedicineLouisiana State University Health Sciences Center

The presynaptic active zone is a dynamic structure that orchestrates regulated release of neurotrans- mitters. Developmental and aging processes, and changes in neuronal network activity can all modulate the number, size and composition of active zone and thereby synaptic efficacy. However, very little is known about the mechanism that controls the structural stability of active zone. By study- ing a model synapse, the Drosophila neuromuscular iunction, our recent work shed light on how two scaffolding proteins at the active zone regulate active zone stability by promoting a localized dephos- phorylation event at the nerve terminal. Here we discuss the major insights from our findings and their implications for future research.

关键词： active zone stability Drosophila neuromuscular junction dephosphorylation Liprin-α Syd-1 PP2A GSK-3β

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Dephosphorylated mutations affect the protein-protein interactions of ERF in Populus simonii x P.nigra

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BIOCELL 2020年第1期44卷 117-126页

作者： Yao SUN Yao LI Xin SUN Qiong WU Lei WANG Institute of Advanced Technology Heilongjiang Academy of SciencesHarbinChina

Phosphorylation is a common type of post-translational modification(PTM).It plays a vital role in many cellular processes.The reversible phosphorylation and dephosphorylation affect protein structures and protein-protein interactions.Previously,we obtained five proteins that interact with ethylene-responsive factor(ERF)from the cDNA library of Populus simonii x Populus nigra.To further investigate the effect of dephosphorylation of PsnERF on its protein binding ability,we generated different phosphorylation states of PsnERF and demonstrated their protein binding capacity by the yeast two-hybrid assay(Y2H).The secondary structures and 3D structures of PsnERF,ERFm,TrunERF,and psnerf^(197/198/202a) were predicted by homology modeling.The Y2H assay indicated that the deletion of serine-rich regions does not affect the interactions,while dephosphorylated mutations blocked the interactions.Homology modeling results suggested that the protein-binding activity was affected by dephosphorylation,and the S197/S198/S202 residues of PsnERF may be the key phosphorylation sites influencing its binding ability.

关键词： dephosphorylation PsnERF Y2H Secondary structure Homology modeling

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Alternation of Na^+-Ca^(2+) exchange in rat cardiac sarcolemmal membranes during different phases of sepsis

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Chinese Medical Journal 2000年第1期113卷 18-21页

作者：王晓红杨军董林旺庞永政苏静怡唐朝枢刘乃奎 Institute of Cardiovascular Research First Hospital Beijing Medical University Beijing 100034 China

Objective To study the alteration of Na + Ca 2+ exchange in rat cardiac sarcolemmal membrane during phases of septic shock Methods Sepsis was induced by cecal ligation and puncture (CLP) Na + Ca 2+ exchange was assayed by radioactive analysis Results Na + dependent 45 Ca 2+ uptake was decreased by 62%-69% in late phase of sepsis, whereas it was not affected in early phase of sepsis Na + Ca 2+ exchange stimulated by 5'guanylyl imidodiphosphate [Gpp(NH)p] was decreased by 65 7% in late phase of sepsis but unaltered in early phase of sepsis Two agonists (angiotensin Ⅱ and phenylephrine) coupled to Gq and a protein kinase C activator, phorbol 12 myristate 13 acetate (PMA) all inhibited Na + Ca 2+ exchange in late phase of sepsis Na + Ca 2+ exchange activities induced by phosphorylation of Na + Ca 2+ exchange were decreased in late phase of sepsis, whereas inhibition of Na + Ca 2+ exchange by dephosphorylation was increased both in early and late phases of sepsis Conclusion The alteration of Na + Ca 2+ exchange during different phases of sepsis might be related to the activities of Gq, protein kinase C, and phosphorylation/dephosphorylation

关键词： Na + Ca 2+ exchange phosphorylation sepsis dephosphorylation

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