Faculty Opinions recommendation of Lymphoid cell growth and transformation are suppressed by a key regulatory element of the gene encoding PU.1.

Recent research suggests that the activation of lipid biosynthesis (lipogenesis) is linked with prostate cancer (PCa) malignancy. Sterol regulatory element-binding protein-1 (SREBP-1) is a key transcriptional regulator controlling lipogenesis. Moreover, androgen receptor (AR) has been well defined to play an important role in lethal PCa aggressiveness from androgen-responsive to castration-resistant status. In this study, we showed that the quality-assured Ganoderma tsugae ethanol extract (GTEE), a Chinese natural and herbal product, significantly inhibited expression of SREBP-1 and its downstream genes associated with lipogenesis in PCa cells. Through inhibiting SREBP-1, GTEE reduced the levels of intracellular fatty acids and lipids in PCa cells. Importantly, GTEE also downregulated the expression of AR and prostate-specific antigen (PSA) in both androgen-responsive and castration-resistant PCa cells. By blocking the SREBP-1/AR axis, GTEE suppressed cell growth and progressive behaviors, as well as activating the caspase-dependent apoptotic pathway in PCa cells. These data provide a new molecular basis of GTEE for the development of a potential therapeutic approach to treat PCa malignancy.

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Viability of clathrin heavy-chain-deficient Saccharomyces cerevisiae is compromised by mutations at numerous loci: implications for the suppression hypothesis.

Molecular and Cellular Biology ◽

10.1128/mcb.11.8.3868 ◽

1991 ◽

Vol 11 (8) ◽

pp. 3868-3878 ◽

Cited By ~ 13

Author(s):

A L Munn ◽

L Silveira ◽

M Elgort ◽

G S Payne

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Growth ◽

Heavy Chain ◽

Secretory Pathway ◽

Genetic Locus ◽

Wild Type ◽

Site Mutation ◽

Gene Encoding ◽

Clathrin Heavy Chain ◽

Lethal Allele

The gene encoding clathrin heavy chain in Saccharomyces cerevisiae (CHC1) is not essential for growth in most laboratory strains tested. However, in certain genetic backgrounds, a deletion of CHC1 (chc1) results in cell death. Lethality in these chc1 strains is determined by a locus designated SCD1 (suppressor of clathrin deficiency) which is unlinked to CHC1 (S. K. Lemmon and E. W. Jones, Science 238:504-509, 1987). The lethal allele of SCD1 has no effect on cell growth when the wild-type version of CHC1 is present. This result led to the proposal that most yeast strains are viable in the absence of clathrin heavy chain because they possess the SCD1 suppressor. Discovery of another yeast strain that cannot grow without clathrin heavy chain has allowed us to perform a genetic test of the suppressor hypothesis. Genetic crosses show that clathrin-deficient lethality in the latter strain is conferred by a single genetic locus (termed CDL1, for clathrin-deficient lethality). By constructing strains in which CHC1 expression is regulated by the GAL10 promoter, we demonstrate that the lethal alleles of SCD1 and CDL1 are recessive. In both cases, very low expression of CHC1 can allow cells to escape from lethality. Genetic complementation and segregation analyses indicate that CDL1 and SCD1 are distinct genes. The lethal CDL1 allele does not cause a defect in the secretory pathway of either wild-type or clathrin heavy-chain-deficient yeast. A systematic screen to identify mutants unable to grow in the absence of clathrin heavy chain uncovered numerous genes similar to SCD1 and CDL1. These findings argue against the idea that viability of chc1 cells is due to genetic suppression, since this hypothesis would require the existence of a large number of unlinked genes, all of which are required for suppression. Instead, lethality appears to be a common, nonspecific occurrence when a second-site mutation arises in a strain whose cell growth is already severely compromised by the lack of clathrin heavy chain.

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Mutation in the Gene Encoding Sterol Regulatory Element Binding Protein (SREBP-2) in Hyper-Cholesterolaemic Subjects

International Journal of Human Genetics ◽

10.1080/09723757.2007.11886012 ◽

2007 ◽

Vol 7 (4) ◽

pp. 315-317 ◽

Cited By ~ 1

Author(s):

Vivek Pratap Singh ◽

Nakul Sinha ◽

V. Ramesh ◽

Satyendra Tewari ◽

Faisal Khan ◽

...

Keyword(s):

Binding Protein ◽

Regulatory Element ◽

Gene Encoding ◽

Element Binding Protein ◽

Sterol Regulatory Element

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A Shared Regulatory Element Controls the Initiation of Tcf7 Expression During Early T Cell and Innate Lymphoid Cell Developments

Frontiers in Immunology ◽

10.3389/fimmu.2020.00470 ◽

2020 ◽

Vol 11 ◽

Author(s):

Christelle Harly ◽

Devin Kenney ◽

Yueqiang Wang ◽

Yi Ding ◽

Yongge Zhao ◽

...

Keyword(s):

T Cell ◽

Lymphoid Cell ◽

Regulatory Element ◽

Innate Lymphoid Cell

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Rapid Depletion of Free Vancomycin in Medium in the Presence of β-Lactam Antibiotics and Growth Restoration in Staphylococcus aureus Strains with β-Lactam-Induced Vancomycin Resistance

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00762-08 ◽

2008 ◽

Vol 53 (1) ◽

pp. 63-68 ◽

Cited By ~ 11

Author(s):

Chie Yanagisawa ◽

Hideaki Hanaki ◽

Hidehito Matsui ◽

Shinsuke Ikeda ◽

Taiji Nakae ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Cell Growth ◽

Culture Medium ◽

Pcr Amplification ◽

Vancomycin Resistance ◽

Gene Encoding ◽

Vancomycin Concentration ◽

Methicillin Resistant ◽

Lactam Antibiotic ◽

Absorption Level

ABSTRACT A class of methicillin-resistant Staphylococcus aureus strains shows vancomycin resistance in the presence of β-lactam antibiotics (β-lactam-induced VAN-resistant methicillin-resistant S. aureus [BIVR]). Two possible explanations may be offered: (i) vancomycin in culture medium is depleted, and (ii) the d-Ala-d-Ala terminal of the peptidoglycan network is replaced with d-Ala-d-lactate. We tested these hypotheses by quantifying free vancomycin in the medium through the course of cell growth and by PCR amplification of the van genes. Growth of the BIVR cells to an absorption level of ∼0.3 at 578 nm required about 24 h in the presence of vancomycin alone at the MIC (4.0 μg/ml). However, growth was achieved in only about 10 h when 1/1,000 to 1/2,000 the MIC of β-lactam antibiotic was added 2 h prior to the addition of vancomycin, suggesting that the β-lactams shortened the time to recovery from vancomycin-mediated growth inhibition. Free vancomycin in the culture medium decreased to 2.3 μg/ml in the first 8 h in the culture containing vancomycin alone, yet cell growth was undetectable. When the vancomycin concentration dropped below ∼1.5 μg/ml at 24 h, the cells began to grow. In the culture supplemented with the β-lactam 2 h prior to the addition of vancomycin, the drug concentration continuously dropped from 4 to 0.5 μg/ml in the first 8 h, and the cells began to grow at a vancomycin concentration of ∼1.7 μg/ml or at 4 h of incubation. The gene encoding the enzyme involved in d-Ala-d-lactate synthesis was undetectable. Based on these results, we concluded that BIVR is attributable mainly to a rapid depletion of vancomycin in the medium triggered or promoted by β-lactam antibiotics.

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LMNA-linked lipodystrophies: from altered fat distribution to cellular alterations

Biochemical Society Transactions ◽

10.1042/bst20110675 ◽

2011 ◽

Vol 39 (6) ◽

pp. 1752-1757 ◽

Cited By ~ 14

Author(s):

Guillaume Bidault ◽

Camille Vatier ◽

Jacqueline Capeau ◽

Corinne Vigouroux ◽

Véronique Béréziat

Keyword(s):

Regulatory Element ◽

Fat Distribution ◽

Premature Aging ◽

Mitogen Activated Protein Kinase ◽

Metabolic Disturbances ◽

Gene Encoding ◽

Partial Lipodystrophy ◽

Metabolic Alterations ◽

Mitogen Activated Protein ◽

Cellular Alterations

Mutations in the LMNA gene, encoding the nuclear intermediate filaments the A-type lamins, result in a wide variety of diseases known as laminopathies. Some of them, such as familial partial lipodystrophy of Dunnigan and metabolic laminopathies, are characterized by lipodystrophic syndromes with altered fat distribution and severe metabolic alterations with insulin resistance and dyslipidaemia. Metabolic disturbances could be due either to the inability of adipose tissue to adequately store triacylglycerols or to other cellular alterations linked to A-type lamin mutations. Indeed, abnormal prelamin A accumulation and farnesylation, which are clearly involved in laminopathic premature aging syndromes, could play important roles in lipodystrophies. In addition, gene expression alterations, and signalling abnormalities affecting SREBP1 (sterol-regulatory-element-binding protein 1) and MAPK (mitogen-activated protein kinase) pathways, could participate in the pathophysiological mechanisms leading to LMNA (lamin A/C)-linked metabolic alterations and lipodystrophies. In the present review, we describe the clinical phenotype of LMNA-linked lipodystrophies and discuss the current physiological and biochemical hypotheses regarding the pathophysiology of these diseases.

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