Control of the translational repressor, PHAS-I, was investigated by expressing proteins with Ser/Thr → Ala mutations in five (S/T)P phosphorylation sites. Results experiments HEK293 cells reveal at least three levels control. At one extreme is nonregulated phosphorylation, exemplified constitutive Ser82. an intermediate level, amino acids and insulin stimulate Thr36, Thr45, Thr69 via mTOR-dependent processes that function independently other sites PHAS-I. third extent site modulates another....

Synthesis of the p53 tumor suppressor and its subsequent activation following DNA damage are critical for protection against tumorigenesis. We previously discovered an internal ribosome entry site (IRES) at 5' untranslated region mRNA. However, connection between IRES-mediated translation p53's suppressive function is unknown. In this study, we identified two IRES trans-acting factors, translational control protein 80 (TCP80), RNA helicase A (RHA), which positively regulate activity....

Abstract Ataxia telangiectasia (A‐T) is an autosomal, recessive disorder mainly characterized by neuronal degeneration. However, the reason for degeneration in A‐T patients still unclear. ATM (A‐T, mutated), gene mutated A‐T, encodes a 370‐kDa protein kinase. We measured levels of found differentiated neuron‐like rat PC12 cells and human SH‐SY5Y cells. that, cells, decreased dramatically after differentiation, which consistent with previous results observed mouse neural progenitor In...

Background: Currently, sorafenib is the only systemic chemotherapy drug for advanced stage Hepatocellular carcinoma (HCC). However, emerging data from some clinical HCC patients indicate that alone has moderate antitumor efficacy, and could not inhibit disease metastasis progression. KU-55933 a specific ATM inhibitor, which pro-apoptotic effect on tumor cells. In this study, we analyzed synergistic of proliferation cell lines. Methods: Three lines were treated with or combination in vitro to...

Synthesis of the p53 tumor suppressor increases following DNA damage. This increase and subsequent activation are essential for protection normal cells against tumorigenesis. We previously discovered an internal ribosome entry site (IRES) that is located at 5′-untranslated region (UTR) mRNA found IRES activity However, mechanism underlying IRES-mediated translation in response to damage still poorly understood. In this study, we translational control protein 80 (TCP80) has increased binding...

Results obtained with PHAS-I proteins having Ser to Ala mutations in the five known phosphorylation sites indicate that mTOR preferentially phosphorylates Thr36 and Thr45. The effects of phosphorylating these on eIF4E binding were assessed a far-Western analysis labeled probe. Phosphorylation only slightly attenuated eIF4E, while Thr45 markedly inhibited binding. neither site affected electrophoretic mobility protein, indicating results studies rely solely gel-shift assay assess changes must...

Abstract Enhanced glucose uptake is coupled with elevated aerobic glycolysis (the Warburg effect) in cancer cells and closely correlated increased tumor aggressiveness poor prognosis. We previously discovered that ATM, a protein kinase deficient Ataxia‐telangiectasia (A‐T) disease, an insulin‐responsive participates insulin‐mediated muscle by stimulating transporter 4 (GLUT4) translocation. However, the role of ATM tumorigenesis unclear. In present study, we found aggressive breast prostate...

The dihydrolipoyl acetyltransferase (E2 component) is a 60-mer assembled via its COOH-terminal domain with exterior E1-binding and two lipoyl domains (L2 then L1) sequentially connected by mobile linker regions. E2 facilitates markedly enhanced function of the pyruvate dehydrogenase kinase (PDK) phosphatase (PDP). Human structures were prepared only one (L1 or L2) alanines substituted at sites lipoylation (Lys-46 in L1 Lys-173 L2). L2 group shown to be essential for PDP required greatly...

Staphylococcus aureus drug resistance to antibiotics is a serious situation that has drawn greater attention immunotherapy and prophylaxis. Peptidoglycan (PGN) common conserved component of the cell wall Gram-positive bacteria such as S. aureus. However, PGN, thymus-independent antigen, cannot be considered vaccine candidate because its very weak immunogenicity. In this study we have attempted enhance immunogenicity PGN by identifying peptide mimic sequence would act thymus-dependent...

The p53 tumor suppressor plays a critical role in protecting normal cells from malignant transformation. Development of small molecules to reactivate cancer has been an area intense research. We previously identified internal ribosomal entry site (IRES) within the 5' untranslated region mRNA that mediates translation independent cap-dependent translation. Our results also show response DNA damage, switch cap-independent mRNA. In present study, we discovered specific inhibitor translation,...

Abstract Background Based on previous findings, we hypothesized that Vasohibin 2 (VASH2) protein may induce epithelial‐mesenchymal transition (EMT) of pancreatic cancer (PC) cells by promoting the malignant behaviors these cells. The present study aimed to test this hypothesis and explore possible mechanisms involved. Methods expression VASH2 in PC tissues cell lines was detected quantitative real‐time PCR Western blot. with overexpression or knockdown were used examine involvement EMT...

Lipids play crucial biological roles in health and disease, including cancers. The phosphatidylinositol 3-kinase (PI3K) signaling pathway is a pivotal promoter of cell growth proliferation various types cancer. somatic mutations PIK3CA, the gene coding for catalytic subunit p110α PI3K, are frequently present cancer cells, breast Although most prominent mutants, represented by single amino acid substitutions helical domain exon 9 (E545K) kinase 20 (H1047R) known to cause gain PI3K function,...

Ataxia-telangiectasia (A-T) is a human autosomal recessive disorder characterized by neuronal degeneration as well many other physiological and somatic defects. ATM (A-T, mutated), the gene mutated in A-T, encodes 370 kDa protein kinase. knockout mouse models (ATM(-/-)) show growth retardation, infertility, neurological dysfunction, defects T-lymphocytes, extreme sensitivity to ionizing radiation. We have recently established multiple ATM(+/-) breeding pairs discovered that all ATM(-/-)...

Objective To study the effects of Leptin on expression CD86 and HLA-DR in human monocytes.Methods The THP-1 Cells primary monocytes were detected by flow cytometry.Results Expression cells was significantly increased after treatment with high-dose ( CD86Untreated group:8.78 ± 1.66,CD86leptin10:50.76 4.29,CD86leptin100:95.20 4.90; HLAUntreated group:20.75 2.12,HLAleptin10:102.14 5.75,HLAleptin100:104.32 4.75;).The similar results observed group:17.91 1.78,CD86leptin100:48.80 3.60; group:34.10...