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Yi Tang

Publications and source records attributed to Yi Tang.

At least 109 records · Page 6Linked to original sources
PubMed2003

[The relationship between ATM gene silence inducing apoptosis susceptibility and abnormal CDK activity].

OBJECTIVE: To explore the molecular elements responsible for the enhanced apoptotic susceptibility in U937 cells mediated by silencing atactic telangiectasis mutation (ATM) gene. METHODS: Two U937 cell mutants, U937-ASPI3K (ATM gene negative) and U937-pZEOSV2 (+) (ATM gene positive) were used as a cell model system. Apoptosis was examined by measuring free nucleosome concentrations in U937 cells. Western blotting was employed to measure nuclear protein abundances of cdc25A, cdc25B, cdc25C, total p34cdc2, p34cdc2 (Thr161) or p34cdc2 (Thr14, Tyr15). RT-PCR was used to estimate cdc25 transcript levels. RESULTS: U937-ASPI3K exhibited an enhanced apoptotic susceptibility to lower dosage of irradiation, which could not be blocked by protein synthesis inhibitor. Protein serine-theronine phosphatase inhibitor or cyclin-dependent kinase (CDK) inhibitors could abolish the enhancement. Upon irradiation, p34cdc2 in U937-pZEOSV2 (+) was in an inactive state owing to phosphorylation of Thr 14 and Tyr15, which was associated with a dramatic decrease of nuclear cdc25A, cdc25B and cdc25C poteins. In contrast, p34cdc2 in U937-ASPI3K was in an active state owing to the low phosphorylation of Thr14 and Tyr15, which was associated with constant nuclear cdc25A, cdc25B and cdc25C protein abundance before and after irradiation. The responsive decrease of nuclear cdc25 proteins occurred at the post-transcription level. CONCLUSION: Silencing ATM gene blocks the irradiation induced responsive decrease of nuclear cdc25 proteins, resulting in an abnormal activation p34cdc2 is the critical molecular mechanism for the enhanced apoptotic responses.

Apoptosis↗
PubMed2003

[Iron status and effect of early iron supplementation on sub-clinical iron deficiency in rural school-age children from mountainous areas of Beijing].

OBJECTIVE: To understand iron nutritional status in school-age children, incidence of the sub-clinical iron deficiency (SID) and effect of iron supplementation on SID in the rural school-age children from mountainous areas of Beijing. METHODS: The dietary survey and food frequency questionnaire survey were conducted in 1,012 school children aged 7 - 13 at rural mountainous areas of Fangshan District, Beijing, and their blood samples were collected for analyzing biochemical indicators for iron nutrition. Two hundred and sixty-seven children with IDs (iron deficiency store) and IDE (iron deficiency erythropoiesis), based on screening criteria for iron-deficiency anemia, received an iron supplementation (NaFeEDTA) capsule (containing 60 mg iron element) weekly, and those with IDA (iron deficiency anemia) received NaFeEDTA capsule thrice weekly for nine weeks. Blood biochemical indicators for iron nutrition were determined repeatedly and compared with those before and after the intervention. RESULTS: The daily average intakes of energy, protein, iron and vitamin C in school children of all age groups reached the daily recommended criteria (> 85% of the RNIs), but the proportion of heme in dietary iron constitution was lower. The average blood biochemical indicators for iron nutrition were as follows: serum ferritin (SF) (50.83 +/- 33.09) micro g/L, free erythrocyte protoporphyrin (FEP) (489.44 +/- 219.61) micro g/L, hemoglobin (Hb) (130.57 +/- 10.82) g/L, and the ratio of FEP/Hb (3.83 +/- 1.96), respectively. Incidence of total iron deficiency in rural children was 26.5%, with proportions of iron deficiency (IDs), iron deficiency erythropoiesis (IDE), and iron deficiency anemia (IDA) of 15.5%, 7.1%, and 3.9% respectively. SID accounted for 85.4% of the total iron deficiency, which was 5.8 times as much as IDA. With iron supplementation for 9 weeks, the hematdogical index of iron increased significantly and returned to the normal level. CONCLUSIONS: The incidence of subclinical iron deficiency in the rural school-age children was insidious and should be attached more importance, which was helpful to its early recognition and intervention. Iron supplementation is important for children with SID to prevent and decrease the occurrence of IDA.

Adolescent↗
PubMed2003

[Transfection of chk1/2 antisense oligonucleotide to HL-60 cell line increases the apoptotic sensitivity to irradiation].

OBJECTIVE: To block signal transduction of cell cycle checkpoints by antisense blocking of chk1/2 gene to increase the radiation sensitivity of HL-60 cell line. METHOD: To transfect the HL-60 cell with chk1/2 antisense and sense chain alone and in combination, expose the cells to irradiation at 24 h after the transfection, the chk1 protein change was assayed by Western blot and the cell cycles and annexin V apoptosis rates by FCM. RESULTS: The irradiated apoptosis sensitivity was increased by antisense blocking of chk1 gene in HL-60 cell line, the apoptotic rate was 26.31% being significantly higher than that of the sense blocking (10.34%) (P < 0.05), Furthermore, the G(2)/M phase blocking phenomenon decreased and a synergic effect was observed in antisense blocking both the chk1 and chk2 genes. CONCLUSION: Antisense blocking of chk1/chk2 could increase the apoptotic sensitivity to irradiation.

Apoptosis↗
PubMed2003

[Relationship between ataxia telangiectasia mutant(ATM) expression of HL-60 and SiHA cell lines and their cell cycle arrest after 60Co radiation].

BACKGROUND & OBJECTIVE: Ataxia telangiectasia is caused by ataxia telangiectasia mutant(ATM) gene and it is characterized by hypersensitivity to the radiation. So the ATM expression should be related to the radiation sensitivity. This study was designed to investigate the relationship between ATM expression in two kinds of tumor cell lines and their cell cycle arrest after irradiation of ionization radiation to explore their self-protection function. METHODS: ATM mRNA and protein expression of HL-60 and SiHA cell lines were measured by semi-quantitive reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry. The cells were irradiated at the dose of 6, 10, and 15 Gy by (60)Co and the change of apoptosis and cell cycle arrest phenomenon at the time of 6, 12, 24, 48, and 60 hours after the radiation were observed. RESULTS: The ATM mean protein fluorescent intensity of HL-60 and SiHA cells were 14.11+/-2.38 and 27.74+/-1.16,respectively. The ATM protein abundance in SiHA was two times more than that in HL-60,and consistent with this, the ATM RNA relative expression of HL-60 and SiHA cells were 0.09 and 0.80, respectively. The ATM transcript levels in SiHA are 9 times more than that in HL-60. The G(2)/M phase arrest after the radiation was observed in both cell lines, whereas SiHA exhibits a much strong cell cycle arrest than HL-60. CONCLUSION: The cell cycle arrest of HL-60 and SiHA cell lines to the irradiation corresponds to their ATM expression levels. The lower ATM expression, the weaker response for cell cycle arrest induced by radiation.

Apoptosis↗
PubMed2003

[Establishment of BAC mediated transgenic mice containing 97 kb beta-globin gene cluster].

OBJECTIVE: To delete IL-11 receptor alpha chain gene from the Bacterial Artificial Chromosome (BAC) chimeric DNA by RecA protein mediated homologous recombination method and establish the transgenic mice model containing whole beta-globin gene cluster. METHODS: Two 500 bp homologous sequences (A and B) located at the upstream and downstream of IL-11 receptor alpha chain gene respectively were cloned into the Hind III and Xba I sites of pBV vector, then the 1 kb A + B fragment was recovered from the building vector and inserted into the Sal I site of the shuttle vector pSV-RecA. After transforming the shuttle vector into the competent DH10B E. Coli containing BAC DNA, the IL-11 receptor alpha chain gene was finally deleted from the BAC DNA through chloramphenicol positive selection and fusaic acid negative selection. The new BAC clone was characterized by Pulse Field Gel Electrophoresis (PFGE). Then, we microinjected the linearized and purified BAC DNA into the mouse fertilized eggs and prepared the transgenic mice. RESULTS: By RecA protein mediated homologous recombination method, we deleted the IL-11 receptor alpha chain gene from the BAC DNA containing the complete beta-globin Gene Cluster and established 3 respective transgenic mice lines. CONCLUSION: Human beta-globin gene cluster in the transgenic mice mediated by new BAC expresses in a correct mode and level as compared with previous transgenic mice.

Animals↗
PubMed2002

Attenuation of the editing activity of the Escherichia coli leucyl-tRNA synthetase allows incorporation of novel amino acids into proteins in vivo.

The fidelity of translation is dependent on the specificity of the aminoacyl-tRNA synthetases (aaRSs). The aaRSs that activate the hydrophobic amino acids leucine, isoleucine, and valine employ a proofreading mechanism that hydrolyzes noncognate aminoacyl adenylates and misaminoacylated tRNAs. Discrimination between structurally similar amino acids by these AARSs is believed to operate by a double-sieve principle, wherein a separate editing domain governs hydrolysis on the basis of the size and hydrophilicity of the amino acid side chain. Leucyl-tRNA synthetase (LeuRS) relies on its editing function to correct misaminoacylation of tRNA(Leu) by isoleucine and methionine. Thr252 of Escherichia coli LeuRS has been shown previously to be important in defining the size of the editing cavity. Here we report the isolation and characterization of three LeuRS mutants with point mutations at this position (T252Y, T252L, and T252F). The proofreading activity of the synthetase is significantly impaired when an amino acid bulkier than threonine is introduced. The rate of misaminoacylation of tRNA(Leu) by isoleucine and valine increases with the increasing size of the amino acid substituent at position 252, and the noncognate amino acids norvaline and norleucine are inserted efficiently at the leucine sites of recombinant proteins under conditions of constitutive overexpression of the T252Y mutant in E. coli. In addition, the unsaturated amino acids allylglycine, homoallylglycine, homopropargylglycine, and 2-butynylalanine all support protein synthesis in E. coli hosts harboring the mutant synthetase. These results demonstrate that programmed manipulation of the editing cavity can allow in vivo incorporation of novel protein building blocks.

Acylation↗
PubMed2002

ELF a beta-spectrin is a neuronal precursor cell marker in developing mammalian brain; structure and organization of the elf/beta-G spectrin gene.

Spectrins play a pivotal role in axonal transport, neurite extension, the organization of synaptic vesicles, as well as for protein sorting in the Golgi apparatus and cell membrane. Among spectrins there is great variability in sequence composition, tissue distribution, and function, with two known genes encoding the alpha-chain, and at least five encoding the beta-chain. It remains unclear as to whether novel beta-spectrins such as elf1-4 are distinct genes or beta-G-spectrin isoforms. The role for ELF in the developing nervous system has not been identified to date. In this study we demonstrate the genomic structure of elf-3, as well as the expression of ELF in the developing mouse brain using a peptide specific antibody against its distinctive amino-terminal end. Full genomic structural analyses reveal that elf-3 is composed of 31 exons spanning approximately 67 kb, and confirm that elf and mouse brain beta-G-spectrin share multiple exons, with a complex form of exon/intron usage. In embryonic stages, E9-12, anti-ELF localized to the primary brain vesicular cells that also labeled strongly with anti-nestin but not anti-vimentin. At E12-14, anti-ELF localized to axonal sprouts in the developing neuroblasts of cortex and purkinje cell layer of the cerebellum, as well as in cell bodies in the diencephalon and metencephalon. Double labeling identified significant co-localization of anti-ELF, nestin and dystrophin in sub ventricular zone cells and in stellate-like cells of the developing forebrain. These studies define clearly the expression of ELF, a new isoform of beta-G-spectrin in the developing brain. Based on its expression pattern, ELF may have a role in neural stem cell development and is a marker of axonal sprouting in mid stages of embryonic development.

Alternative Splicing↗
PubMed2002

Vigilant vectors: adeno-associated virus with a biosensor to switch on amplified therapeutic genes in specific tissues in life-threatening diseases.

There are many life-threatening and chronic diseases in which physiological signals could be used to switch on therapeutic protective genes. We are developing a gene therapy approach in which a systemically injected "vigilant vector" waits for these signals and switches on genes to protect specific tissues with high amplification. The concept of a vigilant vector requires four components. The first component is a safe and stable vector that can be administered by systemic injection and express transgenes in a particular organ or tissue. The adeno-associated virus vector is safe and stable for this purpose. The second component is a reversible gene switch which is a biosensor that can detect certain physiological signals. We are developing a hypoxia switch, based on the oxygen-dependent degradation domain of hypoxia-inducible factor. The third component is a tissue-specific promoter, and we have used the myosin light-chain-2V promoter for specific expression in the heart. The fourth component is an amplification system. For this we have developed a double-plasmid/vector system based on the yeast GAL4 and human transcriptional activator p65 to produce a transactivating fusion protein that binds to a GAL4 activation sequence in an activating plasmid that then expresses high levels of cardioprotective genes.

Acute Disease↗
PubMed2002

Epidermal growth factor receptor and Ink4a/Arf: convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis.

Ink4a/Arf inactivation and epidermal growth factor receptor (EGFR) activation are signature lesions in high-grade gliomas. How these mutations mediate the biological features of these tumors is poorly understood. Here, we demonstrate that combined loss of p16(INK4a) and p19(ARF), but not of p53, p16(INK4a), or p19(ARF), enables astrocyte dedifferentiation in response to EGFR activation. Moreover, transduction of Ink4a/Arf(-/-) neural stem cells (NSCs) or astrocytes with constitutively active EGFR induces a common high-grade glioma phenotype. These findings identify NSCs and astrocytes as equally permissive compartments for gliomagenesis and provide evidence that p16(INK4a) and p19(ARF) synergize to maintain terminal astrocyte differentiation. These data support the view that dysregulation of specific genetic pathways, rather than cell-of-origin, dictates the emergence and phenotype of high-grade gliomas.

Animals↗
PubMed2002

Further understanding of the beta-globin locus regulation at the molecular level: looping or linking models?

The human beta-globin locus is a classic model of the eukaryotic multigene family with tissue- and temporally specific expression. Over the past few years, great advances have been achieved in studies of beta-globin locus regulation. The dominant role of the beta-globin locus control region (LCR) in chromatin opening and developmental switching has been challenged, and elements beyond the LCR have been studied in depth. More recently, the fields of research have been expanded to intergenic transcription, nuclear localization and histone modification. Several models have been proposed to elucidate the regulation mechanism; among them, the looping and linking models are the most prevalent. Different models are the summarization of the observations made at different times and a persuasive model must be based on a systematic understanding of the numerous observations. The objective of this review is to provide an overview of progress in the area of beta-globin regulation and then to discuss models for it.

Cell Nucleus↗
PubMed2002

Feasibility of in vivo multichannel optical imaging of gene expression: experimental study in mice.

PURPOSE: To develop and test a multichannel reflectance imaging system for small animals on the basis of a previously developed single-channel setup. MATERIALS AND METHODS: The imaging system was composed of modular parts, including a light source, excitation filters, emission filters, and a charged-coupled device for recording images. On the basis of generated excitation and absorption spectra of green fluorescent protein (GFP), tricarbocyanine 5.5 (Cy5.5), and indocyanine green (ICG), filters were selected to allow spectral separation and optimize resultant recorded signal. The system was tested by using a combination of the fluorochromes to confirm spectral separation. In vivo tests were performed in nude mice with tumors that expressed cathepsin B, which could be evaluated by using a Cy5.5-based activatable probe and GFP. For each in vivo tumor type and channel, statistical analysis was performed on the basis of signal intensity in the region of interest. RESULTS: The different fluorochromes were readily distinguished with the system; characteristics such as power were determined for all wavelengths. The system demonstrated a linear response for GFP, a monotonic response for Cy5.5 over a range of more than three orders of magnitude of concentration, and a more complex response for ICG. In vivo analysis demonstrated the ability to image GFP expression and cathepsin B expression separately in tumors: As expected, marked differences were observed in GFP-expression imaging between tumor types (1,363 arbitrary units [AU] +/- 236 [SD] vs 110 AU +/- 11 for GFP-positive and GFP-negative tumors, respectively; P <.001), whereas similar cathepsin B expression (1,070 AU +/- 285 vs 1,168 AU +/- 367; P >.5) was observed. Histologic analysis confirmed in vivo findings. CONCLUSION: Imaging multiple gene expressions simultaneously in vivo by using optical imaging is feasible.

Animals↗
PubMed2002

Vigilant vector: heart-specific promoter in an adeno-associated virus vector for cardioprotection.

Repeated bouts of ischemia in the heart lead to fibrosis and eventually to heart failure. Although certain genes, such as SOD or hemoxygenase and antisense to AT(1)R, ACE, and (beta(1)-AR can provide short-term protection of the heart from ischemia, there is no known mechanism for constantly responding to repeated incidences of ischemia. We hypothesized that a "vigilant vector," designed to be expressed specifically in the heart and switch on therapeutic genes only during hypoxia, would provide cardioprotection. To attain cardiac specificity, we inserted an MLC2v promoter into an adeno-associated virus (AAV) designed to deliver AS to AT(1)R and gfp. In in vitro experiments in cardiomyocytes (H9C2 cells), the MLC2v-AAV-gfp drove gene expression in all cells at levels comparable to a cytomegalovirus (CMV) promoter. In in vivo experiments, the rAAV-MLC2v-gfp was injected intravenously into mice or rats. Green fluorescence protein (GFP) DNA was located in kidney, heart (right and left ventricle), lung, adrenal and spleen. GFP mRNA, however, was expressed only in the heart and absent in other tissues. To switch on the rAAV transgene during ischemia, we inserted a hypoxia response element (HRE). This upregulates transcription when O(2) levels are low. Thus, there are 4 components to the vigilant vector; a gene switch (HRE), a heart-specific promoter (MLC2v), a therapeutic gene (AS-AT(1)R) and a reporter gene (gfp). To silence or lower basal level of expression while retaining specificity, we have reduced the length of the MLC2v promoter from 3 kb to 1775 bp or 281 bp. The truncated promoter is equally effective in heart specific expression. Preliminary studies with the rAAV-HRE-gfp in vitro show an increased expression in 1% O(2) in 4 to 6 hours. By adding additional hypoxia-inducible factor (HIFalpha) (5 microg), the MLC2v-gfp expression is increased by 4-fold in 1% O(2). Further amplification of the gene to 400-fold in 1% O(2) can be achieved with a double plasmid. The construct may serve as a prototype "vigilant vector" to switch on therapeutic genes in specific tissue with physiological signals.

Angiotensin Receptor Antagonists↗
PubMed2002

Hypoxia inducible double plasmid system for myocardial ischemia gene therapy.

Coronary artery disease frequently involves repeated bouts of myocardial ischemia. To automatically up-regulate the cardioprotective transgenes under hypoxic ischemia, a "vigilant vector" gene therapy system was developed and tested in a rat embryonic myocardial cell line (H9c2). In the vigilant vector, a hypoxia response element-incorporated promoter was used as a switch to turn on the gene expression in response to hypoxic signal. Furthermore, a novel double plasmid system was designed to elevate the potency of the vigilant vector. Instead of putting the promoter and the reporter gene in the same plasmid (single plasmid system), we separated them into two plasmids: the transactivator plasmid and reporter plasmid (double plasmid system). The hypoxia response element (HRE)-incorporated promoter increased the expression of a chimeric transcription factor consisting of the yeast GAL4 DNA binding domain and the human nuclear (transcription) factor-kappaB (NF-kappaB) p65 activation domain. The powerful chimeric regulator binds specifically to the upstream activating sequence for GAL4 in the reporter plasmid and activates the transcription of the transgene. Our experiments showed that the HRE-mediated expression could quickly increase 2.08 +/- 0.75-fold within 6 hours of hypoxia and further augmented 7.12 +/- 1.52-fold when the hypoxia condition was prolonged to 24 hours. The hypoxia-inducible double plasmid system dramatically amplified the transgene expression under both hypoxia and normoxia by 412.79 +/- 185.27-fold and 205.35 +/- 65.44-fold, respectively, relative to the single plasmid system. From these results, we concluded that this hypoxia inducible double plasmid system could be used therapeutically to switch on genes that have proven beneficial effects in myocardial ischemia.

Analysis of Variance↗
PubMed2002

Biologic characteristics of fibroblast cells cultured from the knee ligaments.

OBJECTIVE: To culture fibroblast cells from the knee ligaments and to study the biological characteristics of these cells. METHODS: Cells of the anterior cruciate ligament (ACL) and the medial collateral ligament (MCL) from New Zealand white rabbit were cultured in vitro. Cellular growth and expression of the collagen were analyzed. Moreover, an in vitro wound closure model was established and the healing of the ACL and the MCL cells was compared. RESULTS: Maximal growth for all these cells were obtained with Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum, but RPMI 1640 and Ham's F12 media were not suitable to maintain these cells. Morphology of both ACL and MCL cells from New Zealand white rabbit was alike in vitro, but the MCL cells grew faster than the ACL cells. Both cell types produced similar amount of collagen in culture, but the ratio of collage type I to type III produced by ACL cells was higher than that produced by MCL cells. Wound closure assay showed that at 36 hours after injury, cell-free zones created in the ACL cultures were occupied partially by the ACL cells; in contrast, the wounded zone in the MCL cultures was almost completely covered by the cells. CONCLUSIONS: Although the ACL cells and the MCL cells from New Zealand white rabbit show similar appearance in morphology in culture, the cellular growth and the biochemical synthesis of collagen as well as the healing in vitro were significantly different. These differences in intrinsic properties of the two types of cells in vitro might contribute to the differential healing potentials of these ligaments in vivo.

Animals↗
PubMed2002

Molecular mechanism of enhanced apoptotic response in U937 cells mediated by sodium butyrate.

OBJECTIVE: To study the effects of sodium butyrate (NaBu) on cell cycle checkpoint and the apoptosis sensitivity in U937 cells. METHODS: Two mutant U937 cell lines, U937-ASPI3K (ATM negative) and U937-pZeosv2(+) (ATM wild-type), were used as the cell model system. Immunoprecipitation and kinase assay were used to examine the p38 MAPK and ERK1 kinase activities. Western blot was used to analyze the phosphorylation of Bad protein. RESULTS: U937-pZeosv2(+) pretreated with NaBu exhibited enhanced apoptotic response in a NaBu dose dependent fashion upon (137)Cs irradiation, which could be abolished by olomoucine (OLM), a p38 MAPK specific inhibitor. On the other hand, Cyclin dependent kinase 2 (CDK2) specific inhibitor CDK2-I and p34cdc2/cyclinB inhibitor alsterpaullone (ALP) failed to block the effects of NaBu. Similar results were also observed in U937-ASPI3K. The effect of irradiation on p38 MAPK and ERK1 was strikingly potentiated by NaBu. Furthermore, inactivation of irradiated Bad protein via phosphorylation on serine 136 was also enhanced. CONCLUSION: NaBu is able to enhance the apoptotic response in U937 cells, which is mediated by p38 MAPK activation but not ATM status.

Apoptosis↗
PubMed2002

[Variation of plasma folate levels in adults between some areas and different seasons in China].

OBJECTIVE: To describe the distribution of plasma folate concentrations and prevalence of folate deficiency in adults aged 35 to 64 years in some areas and different seasons in China. METHODS: Study subjects were sampled from the representative rural and urban areas in the south and north of China aged 35 to 64 years totaling 2 545, and their plasma folate concentrations were determined and analyzed. RESULTS: Plasma concentrations of folate in the southern population were significantly higher (16.9 nmol/L) than those in the north (8.3 nmol/L), and the prevalence of folate deficiency in the south (5.8%) was significantly lower than that in the north (37.1%). Plasma folate concentration varied with season either in the south or north. Plasma concentrations of folate were lower during the summer and the fall (15.0 nmol/L) than those during the winter and the spring (18.8 nmol/L) in the south, but without significant changes in the prevalence of folate deficiency in different seasons. However, the plasma folate concentrations were significantly higher during the summer and the fall (9.7 nmol/L) than those during the winter and the spring (7.1 nmol/L) in the north. And the prevalence of folate deficiency in the north was significantly higher in winter and spring (48.0%) than that in summer and fall (26.2%). CONCLUSIONS: There existed significant difference in plasma folate concentrations in adults between varied geographic areas in China, which differed from their seasonal changes.

Adult↗
PubMed2002

[ATM and Cancer].

The mutation of AT gene (ATM) leads to the AT disease (ataxia telangiectasis), the cancer incidence of AT patients and its carriers are significantly higher than the normal persons. And they are easy to have lymphoid tumors, including the lymphoma and leukemia et al. These indicate the ATM play a important role in the cancers pathogenesis mechanism. The ATM gene locate in the human chromosome 11q22-23, and the ATM is a kind of nuclear protein, its major functional domain is P13K (phosphatidylinositol 3-kinase), locates on the carboxy terminus. ATM protein plays a critical role in the signal transduction of cell cycle checkpoint, the repair of damaged DNA and the apoptosis. The mutation of the ATM gene leads to the functional and structural change of ATM protein in the AT patient, then leads to the abnormality of cell cycle checkpoint and the DNA damage repair, the apoptosis sensitivity increase. So the AT patients and their cells are radiosensitive, the characteristic of AT patient suggests the ATM gene is valuable in the cancer's gene therapy

Ataxia Telangiectasia↗