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1.
G3 (Bethesda) ; 10(9): 2999-3008, 2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32737065

RESUMO

Genetic approaches in Drosophila have successfully identified many genes involved in regulation of growth control as well as genetic interactions relevant to the initiation and progression of cancer in vivo Here, we report on large-scale RNAi-based screens to identify potential tumor suppressor genes that interact with known cancer-drivers: the Epidermal Growth Factor Receptor and the Hippo pathway transcriptional cofactor Yorkie. These screens were designed to identify genes whose depletion drove tissue expressing EGFR or Yki from a state of benign overgrowth into neoplastic transformation in vivo We also report on an independent screen aimed to identify genes whose depletion suppressed formation of neoplastic tumors in an existing EGFR-dependent neoplasia model. Many of the positives identified here are known to be functional in growth control pathways. We also find a number of novel connections to Yki and EGFR driven tissue growth, mostly unique to one of the two. Thus, resources provided here would be useful to all researchers who study negative regulators of growth during development and cancer in the context of activated EGFR and/or Yki and positive regulators of growth in the context of activated EGFR. Resources reported here are available freely for anyone to use.


Assuntos
Proteínas de Drosophila , Neoplasias , Animais , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Genes Supressores de Tumor , Neoplasias/genética , Proteínas Nucleares/genética , Transdução de Sinais , Transativadores/metabolismo
2.
FEMS Microbiol Lett ; 363(11)2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27190284

RESUMO

Vitamin C is known to inhibit mycobacterial growth by acting as a hypoxia inducing agent. While investigating how mycobacteriophage growth is influenced by hypoxic conditions induced by vitamin C, using Mycobacterium smegmatis- mycobacteriophage D29 as a model system, it was observed that prior exposure of the host to such conditions resulted in increased burst size of the phage. Vitamin C pre-exposure was also found to induce synchronous growth of the host. A mutant defective in DevR, the response regulator that controls hypoxic responses in mycobacteria, neither supported higher phage bursts nor was it able to undergo synchronized growth following vitamin C pre-exposure, indicating thereby that the two phenomena are interrelated. Further evidence supporting such an interrelationship was obtained from the observation that phage burst sizes varied depending on the stage of synchronous growth that the host cells were in, at the time of infection-higher bursts were observed in the resting/synthetic phases and lower in the dividing ones. The effects were specific in nature as synchronization by an unrelated method, known as 'crowding', did not lead to the same consequence. The results indicate that growth synchronization induced by vitamin C treatment is a DevR-dependent phenomenon which is exploited by mycobacteriophage D29 to grow in larger numbers.


Assuntos
Ácido Ascórbico/farmacologia , Proteínas de Bactérias/metabolismo , Micobacteriófagos/fisiologia , Mycobacterium smegmatis/crescimento & desenvolvimento , Mycobacterium smegmatis/fisiologia , Proteínas Quinases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Ligação a DNA , Regulação Bacteriana da Expressão Gênica , Mutação , Proteínas Quinases/genética
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