Inhibition of Mycobacterial Infection by the Tumor Suppressor PTEN

Huang, Guochang; Redelman-Sidi, Gil; Rosen, Neal; Glickman, Michael S.; Jiang, Xuejun

doi:10.1074/jbc.m112.351940

Cited by 40 publications

(47 citation statements)

References 30 publications

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“…Such preferential colonization of tumor tissue by prokaryotes may be attributed to: (i) aberrant vascularization, (ii) an increased nutrient availability (due to necrotic tissue) at the tumor site, and/or (iii) tumor-directed bacterial chemotaxis (13). In addition, Huang et al (24) demonstrated that the tumor suppressor phosphatase and tensin homolog that is frequently mutated or deleted in various human cancers, is also implicated in the cellular defense against mycoplasmas and mycobacteria, which may therefore increase the susceptibility of tumor cells to a mycoplasma infection.…”

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confidence: 99%

Nucleoside-catabolizing Enzymes in Mycoplasma-infected Tumor Cell Cultures Compromise the Cytostatic Activity of the Anticancer Drug Gemcitabine

Voorde

Sabuncuoğlu

Noppen

et al. 2014

Journal of Biological Chemistry

123

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Background: Gemcitabine is used to treat solid tumors. Some mycoplasmas preferentially colonize tumors in patients. Results: Mycoplasma-encoded cytidine deaminase and pyrimidine nucleoside phosphorylase compromise the cytostatic/antitumor activity of gemcitabine in mycoplasma-infected tumor cell cultures and xenografts in mice. Conclusion: Tumor-associated mycoplasmas may decrease the therapeutic efficiency of gemcitabine. Significance: Current treatment of mycoplasma-infected tumors with gemcitabine may be suboptimal.

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mentioning

confidence: 99%

Nucleoside-catabolizing Enzymes in Mycoplasma-infected Tumor Cell Cultures Compromise the Cytostatic Activity of the Anticancer Drug Gemcitabine

Voorde

Sabuncuoğlu

Noppen

et al. 2014

Journal of Biological Chemistry

123

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“…The Akt has an essential role in invasion and reproduction of several microorganisms (16). Akt1 has several polymorphisms that many of them have been associated with several diseases such as Parkinson's disease, Schizophrenia, and bipolar disorder (7,16). By the time of submission of this manuscript, there was only one report regarding the association of Akt1 polymorphisms and TB and this was the first report from Iran.…”

Section: Discussionmentioning

confidence: 97%

“…They demonstrated that in mac-rophages, a particular tiny particle inhibitor of Akt1 could considerably reduce proliferation of M. tuberculosis (17). The result of Akt1 inhibition is induction of phagosome conversion to phagolysosomes and destruction of the intracellular bacteria (16). In a study on Chinese population, Wang et al (11) found that in patients with PTB, IVS3+18 C⁄C genotype was lower than controls and the patients with PTB had higher C⁄T genotype in contrast to the control group.…”

Section: Discussionmentioning

confidence: 99%

“…In many cell types, Akt influences survival and arrests apoptosis through some stimuli such as retrieve of growth factor and anoikis (9). The Akt has an essential role in invasion and reproduction of several microorganisms (16). Akt1 has several polymorphisms that many of them have been associated with several diseases such as Parkinson's disease, Schizophrenia, and bipolar disorder (7,16).…”

Section: Discussionmentioning

confidence: 99%

“…Previous researches demonstrated that polymorphism in this gene alters expression or activity of Akt1 (18). Huang et al (16) showed mycobacterium infection induced phosphorylation of the host cell Akt and restraint of Akt activity decreased dosage of intracellular infection. Moreover, they demonstrated that Akt postponed phagosomal-lysosomal fusion and therefore, increased intracellular survival of the mycobacteria (16).…”

Section: Discussionmentioning

confidence: 99%

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Genetic Variation in Akt1 and Risk of Tuberculosis Among Iranian Population

et al. 2014

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Background: Tuberculosis (TB) is one of the earliest human diseases which still is considered a public health problem. Both genetic and environmental factors may contribute the susceptibility to tuberculosis. Objectives: Akt is a serine/threonine kinase that has an important role in several cellular processes such as cell cycle control, cell survival, and cellular immigration. The Akt signaling pathway has an essential function in incursion and reproduction of numerous bacteria. Polymorphisms in the Akt genes are known to be related with outcome of infections. We investigated a possible association between Akt1 726 G/A polymorphism and pulmonary tuberculosis (PTB) in Iranian patients with PTB. Analysis of the data was done using χ2, and independent sample t-test. Genotypes analysis between the groups was done using logistic regression analyses. Patients and Methods: This case-control study was performed on 156 patients with pulmonary tuberculosis and 154 healthy controls. For detection of polymorphism, we used tetra amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) and for determination of PCR products size, we used agarose gel electrophoresis. Results: Frequencies of genotypes GG, GA, and AA of the Akt1 726 G/A polymorphism were 45.6%, 47.4%, and 7% in the patients with pulmonary tuberculosis, and 53.9%, 37.0% and 9.1% in the control group, respectively. G allele frequency was 69.2% in patients with PTB and 72.4% in healthy controls. We observed no significant difference in allele and genotype frequencies of the Akt1 polymorphism between patients with PTB and healthy controls. Conclusions: Our finding showed that Akt1 726 G/A polymorphism was not associated with risk of PTB in our population. More studies are necessary to validate our results.

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Automated docking studies provide insights into molecular determinants of ligand recognition by N‐acetyl‐1‐d‐myo‐inosityl‐2‐amino‐2‐deoxy‐α‐d‐glucopyranoside deacetylase (MshB)

Huang¹,

Hernick²

2014

Biopolymers

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The metal-dependent deacetylase N-acetyl-1-D-myo-inosityl-2-amino-2-deoxy-α-D-glucopyranoside deacetylase (MshB) catalyzes the deacetylation of N-acetyl-1-D-myo-inosityl-2-amino-2-deoxy-α-D-glucopyranoside (GlcNAc-Ins), the committed step in mycothiol (MSH) biosynthesis. MSH is the thiol redox buffer used by mycobacteria to protect against oxidative damage and is involved in the detoxification of xenobiotics. As such, MshB is a target for the discovery of new drugs to treat tuberculosis (TB). While MshB substrate specificity and inhibitor activity have been probed extensively using enzyme kinetics, information regarding the molecular basis for the observed differences in substrate specificity and inhibitor activity is lacking. Herein we begin to examine the molecular determinants of MshB substrate specificity using automated docking studies with a set of known MshB substrates. Results from these studies offer insights into molecular recognition by MshB via identification of side chains and dynamic loops that may play roles in ligand binding. Additionally, results from these studies suggest that a hydrophobic cavity adjacent to the active site may be one important determinant of MshB substrate specificity. Importantly, this hydrophobic cavity may be advantageous for the design of MshB inhibitors with high affinity and specificity as potential TB drugs.

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Inhibition of Mycobacterial Infection by the Tumor Suppressor PTEN

Cited by 40 publications

References 30 publications

Nucleoside-catabolizing Enzymes in Mycoplasma-infected Tumor Cell Cultures Compromise the Cytostatic Activity of the Anticancer Drug Gemcitabine

Nucleoside-catabolizing Enzymes in Mycoplasma-infected Tumor Cell Cultures Compromise the Cytostatic Activity of the Anticancer Drug Gemcitabine

Genetic Variation in Akt1 and Risk of Tuberculosis Among Iranian Population

Automated docking studies provide insights into molecular determinants of ligand recognition by N‐acetyl‐1‐d‐myo‐inosityl‐2‐amino‐2‐deoxy‐α‐d‐glucopyranoside deacetylase (MshB)

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