1.Progress of TSC-22 gene research.
Journal of Central South University(Medical Sciences) 2011;36(7):592-596
Transformation growth factor β -inducible gene 22 (TSC-22) is a putative negative growth regulation and tumor suppressor gene. It has the ability to combine with other transcription factors to regulate the cell growth and apoptosis. TSC-22 is lowly expressed in many types of tumors,which may be related to the tumorgenesis and development.
Animals
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Genes, Tumor Suppressor
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Humans
;
Leucine Zippers
;
genetics
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Neoplasms
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physiopathology
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Repressor Proteins
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genetics
;
physiology
;
Transcription Factors
2.SoxD Transcription Factors: Multifaceted Players of Neural Development.
International Journal of Stem Cells 2016;9(1):3-8
SoxD transcription factor subfamily includes three members, Sox5, Sox6, and Sox13. Like other Sox genes, they contain the High-Mobility-Group (HMG) box as the DNA binding domain but in addition feature the subgroup-specific leucine zipper motif. SoxD genes are expressed in diverse cell types in multiple organs during embryogenesis and in adulthood. Among the cells expressing them are those present in the developing nervous system including neural stem (or progenitor) cells as well as differentiating neurons and oligodendrocytes. SoxD transcription factors do not contain distinct activator or repressor domain, and they are believed to function in modulation of other transcription factors in promoter- specific manners. This brief review article will attempt to summarize the latest studies on the function of SoxD genes in embryogenesis with a particular emphasis on the regulation of neural development.
DNA
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Embryonic Development
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Female
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Leucine Zippers
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Nervous System
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Neural Stem Cells
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Neurons
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Oligodendroglia
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Pregnancy
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SOXD Transcription Factors*
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Transcription Factors
3.Engagement of CD99 Reduces AP-1 Activity by Inducing BATF in the Human Multiple Myeloma Cell Line RPMI8226.
Minchan GIL ; Hyo Kyung PAK ; Seo Jeong PARK ; A Neum LEE ; Young Soo PARK ; Hyangsin LEE ; Hyunji LEE ; Kyung Eun KIM ; Kyung Jin LEE ; Dok Hyun YOON ; Yoo Sam CHUNG ; Chan Sik PARK
Immune Network 2015;15(5):260-267
CD99 signaling is crucial to a diverse range of biological functions including survival and proliferation. CD99 engagement is reported to augment activator protein-1 (AP-1) activity through mitogen-activated protein (MAP) kinase pathways in a T-lymphoblastic lymphoma cell line Jurkat and in breast cancer cell lines. In this study, we report that CD99 differentially regulated AP-1 activity in the human myeloma cell line RPMI8226. CD99 was highly expressed and the CD99 engagement led to activation of the MAP kinases, but suppressed AP-1 activity by inducing the expression of basic leucine zipper transcription factor, ATF-like (BATF), a negative regulator of AP-1 in RPMI8226 cells. By contrast, engagement of CD99 enhanced AP-1 activity and did not change the BATF expression in Jurkat cells. CD99 engagement reduced the proliferation of RPMI8226 cells and expression of cyclin 1 and 3. Overall, these results suggest novel CD99 functions in RPMI8226 cells.
Breast Neoplasms
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Cell Line*
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Cyclins
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Humans*
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Jurkat Cells
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Leucine Zippers
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Lymphoma
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Multiple Myeloma*
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Phosphotransferases
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Transcription Factor AP-1*
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Transcription Factors
4.Bovine adenovirus type 3 virions cannot be rescued in vivo after full-length viral genome transfection in the absence of detectable polypeptide IX.
Peng ZHANG ; Qinghong XUE ; Jing MA ; Jingjing REN ; Shuili XIA ; Lu ZHANG ; Wenbin WANG ; Suresh K TIKOO ; Enqi DU
Journal of Veterinary Science 2017;18(2):217-227
Bovine adenovirus type 3 (BAdV3) is being used in the development of potential vehicles for gene therapy and vectored vaccine. To that end, a more comprehensive description of BAdV3 biology is essential. In this study, we focused on the role of pIX in BAdV3 virion rescue after full-length BAdV3 genome transfection. Initially, pIX deletion or initiation codon mutation abolished the production of progeny virions, which suggested that pIX was essential for the rescue of BAdV3 containing a full-length genome. Moreover, through transfection of a panel of pIX mutant BAdV3 genomes, we observed that the conserved N-terminus and the putative leucine zipper element (PLZP) were essential for virion rescue, whereas the C-terminus following the coiled-coil domain was non-essential. In addition, swap of the PLZP element and its following region of BAdV3 pIX to corresponding domains of human adenovirus type 5 (HAdV5) did not affect virion production, whereas swap of the entire pIX abolished production of progeny virions. We suggest that failure of the full-length BAdV3 pIX swap might be due to species specificity of its N-terminus region before the PLZP element.
Adenoviridae*
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Adenoviruses, Human
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Biology
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Codon, Initiator
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Genetic Therapy
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Genome
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Genome, Viral*
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Leucine Zippers
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Species Specificity
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Transfection*
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Virion*
5.Detection of point mutation at C-terminal region of phagosomal coat protein (TACO) in patients with leprosy.
Se Kon KIM ; Tae Jin KANG ; Byoung Chul KIM ; Gue Tae CHAE
Korean Leprosy Bulletin 2003;36(1):11-26
Mycobacteria, which are highly successful pathogen, resist delivary to lysosomes and instead survive within a specialized vacuole, the mycobacterial phagosome. The bacteria survive intracellularly because they are able to actively recruit and retain TACO ( tryptophane aspartate-containing coat protein ) at the mycobacterial phagosome, where it prevents lysosomal delivary in a cholesterol-dependent manner. In this study, we investigated the difference of TACO expression is whether related to mutant in coro1a gene in patients with leprosy and normal volunteer. First, we screened for detection of a mutant in the leucine zipper motif within the exon 11, and then in the exon 9 to 10, and finally in the coiled-coil region. Interestingly, single base substitutions ( point mutation ) presents at assembly site of U1 snRNP, around of 5' splice site in the intron 9, there are a C to T and G to A transition are at 9 bp and 14 bp downstream of 5' splice site, respectively, and both of it. Among the 3 types of polymorphism, frequency of a G to A transition is markedly increased in patients of lepromatous type, which are new cases or relapsed. Both a C to T and G to A transitions are found in 1 case of tuberculoid type and 2 cases in lepromatoue type, but not found in control group. The silent mutation in leucine zipper motif within the exon 11 is located at codon at 454 ( CTG-->CTA), which is 1st leucine from C-terminal among four leucine zipper. In coiled-coil region, no mutation is found in genomic DNA of patients with leprosy. Further, we will do functional study about the identified point mutation and will screen any possible mutation in the region of promotor and WD repeat.
Bacteria
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Codon
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DNA
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Exons
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Healthy Volunteers
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Humans
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Introns
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Leprosy*
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Leucine
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Leucine Zippers
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Lysosomes
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Phagosomes
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Point Mutation*
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Ribonucleoprotein, U1 Small Nuclear
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RNA Splice Sites
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Tryptophan
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Vacuoles
6.Association Study of FOS-Like Antigen-2 Promoter Polymorphisms With Papillary Thyroid Cancer in Korean Population.
Seung Woo KIM ; Choon Dong KIM ; Joo Ho CHUNG ; Kee Hwan KWON
Clinical and Experimental Otorhinolaryngology 2014;7(1):42-46
OBJECTIVES: FOS-like antigen-2 (FOSL-2), a member of the FOS gene family, encode leucine zipper proteins that can heterodimerize with proteins of Jun family. Thus, activating protein (AP)-1 transcription factor is formed, has a crucial role in proliferation, differentiation and apoptosis of normal tissue as well as oncogenic transformation and progression. We performed an association study of single nucleotide polymorphisms (SNPs) in the FOSL-2 with papillary thyroid cancer (PTC). We also estimated the relationships between the SNPs and the clinicopathologic characteristics of PTC. METHODS: One promoter SNPs (rs925255) of FOSL-2 gene were genotyped with direct sequencing method in 94 PTC and 213 controls. PTC patients were dichotomized and compared with respect to clinical parameters of PTC. Genetic data were analyzed using Helixtree, SNPAnalyzer, SNPStats. Multivariate logistic regression analysis was fulfilled to evaluate the genetic effect with adjustment for age and sex. RESULTS: SNP (rs925255) in FOSL-2 showed a significant association (codominant 1 model [G/G vs. A/G]: odds ratio [OR], 0.531, 95% confidence interval [CI], 0.293 to 0.96, P=0.036; dominant model: OR, 0.50, 95% CI, 0.28 to 0.89, P=0.015) with PTC. The frequency of allele G in rs925255 was also significantly associated with PTC (OR, 0.59; 95% CI, 0.34 to 0.91; P=0.02). But we fail to prove significant association between this polymorphism (rs925255) and clinico-pathological parameters. CONCLUSION: Our findings suggest that the rs925255 SNP and its allele G show significant association with the PTC in Korean population.
Alleles
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Apoptosis
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Genes, fos
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Humans
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Leucine Zippers
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Logistic Models
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Methods
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Odds Ratio
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Polymorphism, Single Nucleotide
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Thyroid Gland*
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Thyroid Neoplasms*
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Transcription Factors
7.Evaluation of the role of TAX, HBZ, and HTLV-1 proviral load on the survival of ATLL patients.
Mohammad Mehdi AKBARIN ; Abbas SHIRDEL ; Alireza BARI ; Seyedeh Tahereh MOHADDES ; Houshang RAFATPANAH ; Ehsan Ghayour KARIMANI ; Kobra ETMINANI ; Amin GOLABPOUR ; Reza TORSHIZI
Blood Research 2017;52(2):106-111
BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with very poor prognosis and short survival, caused by the human T-lymphotropic virus type-1 (HTLV-1). The HTLV-1 biomarkers trans-activator x (TAX) and HTLV-1 basic leucine zipper factor (HBZ) are main oncogenes and life-threatening elements. This study aimed to assess the role of the TAX and HBZ genes and HTLV-1 proviral load (PVL) in the survival of patients with ATLL. METHODS: Forty-three HTLV-1-infected individuals, including 18 asymptomatic carriers (AC) and 25 ATLL patients (ATLL), were evaluated between 2011 and 2015. The mRNA expression of TAX and HBZ and the HTLV-1 PVL were measured by quantitative PCR. RESULTS: Significant differences in the mean expression levels of TAX and HBZ were observed between the two study groups (ATLL and AC, P=0.014 and P=0.000, respectively). In addition, the ATLL group showed a significantly higher PVL than AC (P=0.000). There was a significant negative relationship between PVL and survival among all study groups (P=0.047). CONCLUSION: The HTLV-1 PVL and expression of TAX and HBZ were higher in the ATLL group than in the AC group. Moreover, a higher PVL was associated with shorter survival time among all ATLL subjects. Therefore, measurement of PVL, TAX, and HBZ may be beneficial for monitoring and predicting HTLV-1-infection outcomes, and PVL may be useful for prognosis assessment of ATLL patients. This research demonstrates the possible correlation between these virological markers and survival in ATLL patients.
Adult
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Biomarkers
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Human T-lymphotropic virus 1*
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Humans
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Leucine Zippers
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Leukemia-Lymphoma, Adult T-Cell*
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Oncogenes
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Polymerase Chain Reaction
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Prognosis
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RNA, Messenger
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T-Lymphocytes
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Taxes*
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Trans-Activators
8.Expression of a Functional zipFv Antibody Fragment and Its Fusions with Alkaline Phosphatase in the Cytoplasm of an Escherichia coli.
Byung Ung HUR ; Hyo Jung CHOI ; Jae Bong YOON ; Sang Hoon CHA
Immune Network 2010;10(2):35-45
BACKGROUND: Expression of recombinant antibodies and their derivatives fused with other functional molecules such as alkaline phosphatase in Escherichia coli is important in the development of molecular diagnostic reagents for biomedical research. METHODS: We investigated the possibility of applying a well-known Fos-Jun zipper to dimerize V(H) and V(L) fragments originated from the Fab clone (SP 112) that recognizes pyruvate dehydrogenase complex-E2 (PDC-E2), and demonstrated that the functional zipFv-112 and its alkaline phosphatase fusion molecules (zipFv-AP) can be produced in the cytoplasm of Origami(DE3) trxB gor mutant E. coli strain. RESULTS: The zipFv-AP fusion molecules exhibited higher antigen-binding signals than the zipFv up to a 10-fold under the same experimental conditions. However, conformation of the zipFv-AP seemed to be influenced by the location of an AP domain at the C-terminus of V(H) or V(L) domain [zipFv-112(H-AP) or zipFv-112(L-AP)], and inclusion of an AraC DNA binding domain at the C-terminus of V(H) of the zipFv-112(L-AP), termed zipFv-112(H-AD/L-AP), was also beneficial. Cytoplasmic co-expression of disulfide-binding isomerase C (DsbC) helped proper folding of the zipFv-112(H-AD/L-AP) but not significantly. CONCLUSION: We believe that our zipFv constructs may serve as an excellent antibody format bi-functional antibody fragments that can be produced stably in the cytoplasm of E. coli.
Alkaline Phosphatase
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Antibodies
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Clone Cells
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Cytoplasm
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DNA
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Escherichia
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Escherichia coli
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Immunoglobulin Fragments
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Indicators and Reagents
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Leucine Zippers
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Oxidoreductases
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Pathology, Molecular
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Pyruvic Acid
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Sprains and Strains
9.Effect of MITF-M and MITF-A Overexpression on the Dendrtic Formation in Melanocytes.
In Sook JO ; Kyung Cheol SOHN ; Chang Deok KIM ; Young Ho LEE
Korean Journal of Physical Anthropology 2016;29(1):27-34
The microphthalmia-associated transcription factor (MITF), has been described as the master regulator of the basic helix-loop-helix leucine zipper family, involves melanogenesis in melanocytes. MITF consists of at least six isoforms, called MITF-M, MITF-A, MITF-B, MITF-C, MITF-H, and MITF-J. Previously, we found that not only MITF-M is expressed in the human hair follicle, but also MITF-A, MITF-C, MITF-H, and MITF-J isoforms are expressed in the skin. The aim of this study was to conform the MITF isoforms expressed in human skin, and investigate novel role of MITF isoforms in the melanocytes. Expression of MITF-M and MITF-A was found in primary melanoctyes and the melanoma cell lines. Interestingly, when MITF-M and MITF-A were overexpressed in the SK-MEL-24 melanoma cells by adenoviral transfection, length of the dendrites, serves as the principal conduit for melanosomes transfer, was significantly increased in the MITF-M overexpressed cells compared with the control group, and number of the dendtrites was significantly increased in the MITF-A overexpressed cells. A signal molecule involve in actin polymerization during dendrite formation, Rac1, was increased in the SK-MEL-24 melanoma cells treated with adenoviral MITF-M and MITF-A vectors. These results suggest that MITF-M and MITF-A induce dendrite formation via Rac1 signaling in the melanocytes.
Actins
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Cell Line
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Dendrites
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Hair Follicle
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Humans
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Leucine Zippers
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Melanocytes*
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Melanoma
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Melanosomes
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Microphthalmia-Associated Transcription Factor
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Polymerization
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Polymers
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Protein Isoforms
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Skin
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Transfection
10.Preparation and identification of soluble trimeric CD40-isoleucine zipper fusion protein.
Li-Hui XU ; Yi LIU ; Xian-Hui HE
Chinese Journal of Biotechnology 2006;22(3):477-482
The interaction of CD40 with its cognate ligand, CD40L (CD154), plays important roles in immune responses. Blockade of CD40-CD40L signal pathway can protect the progression of antibody- and cell-mediated autoimmune diseases, and reduce allograft rejection thus prolonging graft survival, even engendering long-lived antigen-specific tolerance. The present study aims to enhance the binding activity of CD40 by incorporating an isoleucine zipper (IZ) trimeric motif into CD40 ectodomain to promote the formation of soluble CD40 trimers, which would be useful for blocking CD40-CD40L interaction. A prokaryotic expression vector for soluble human CD40 ectodomain fused with an IZ motif and a hexa-histidine (His6) tag at its carboxyl terminus (sCD40IZ) was constructed by multiple round PCR using cloned CD40 cDNA as a template. The recombinant sCD40IZ protein was expressed highly in Escherichia coli (E. coli) with a molecular weight of 27kD, which is consistent with its theoretical value. It mainly existed in inclusion bodies. After refolding from inclusion bodies, soluble sCD40IZ protein was purified by gel filtration. Its molecular weight in solution was about 91kD when determined by gel filtration, suggesting that it most probably existed in the form of trimers. Moreover, this protein could bind to CD40L expressed on Jurkat T cells and its binding activity was significantly higher than that of soluble CD40 without an IZ motif. These results suggest that incorporation of an IZ motif at the carboxyl terminus of soluble CD40 can facilitate the formation of trimers and enhance its binding activity with CD40L. Thus, the trimeric CD40 protein may be used to block CD40-CD40L signal pathway, suggesting that it may have potential application in preventing autoimmune diseases and transplantation rejection.
CD40 Antigens
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biosynthesis
;
genetics
;
metabolism
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CD40 Ligand
;
metabolism
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Escherichia coli
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genetics
;
metabolism
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Humans
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Isoleucine
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biosynthesis
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genetics
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Leucine Zippers
;
genetics
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Protein Multimerization
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Recombinant Fusion Proteins
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biosynthesis
;
genetics
;
metabolism