scholarly journals A Drosophila RNA helicase gene, pitchoune, is required for cell growth and proliferation and is a potential target of d-Myc

Development ◽  
1998 ◽  
Vol 125 (18) ◽  
pp. 3571-3584 ◽  
Author(s):  
S. Zaffran ◽  
A. Chartier ◽  
P. Gallant ◽  
M. Astier ◽  
N. Arquier ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Ribosome Biogenesis ◽  
Protein Biosynthesis ◽  
Ectopic Expression ◽  
Rna Helicase ◽  
Potential Target ◽  
Dead Box ◽  
First Instar ◽  
Cell Growth And Proliferation

This article describes the characterization of a new Drosophila gene that we have called pitchoune (pit) (meaning small in Provence) because mutations in this gene produce larvae that cannot grow beyond the first instar larval stage although they can live as long as 7–10 days. All the tissues are equally affected and the perfectly shaped larvae are indistinguishable from first instar wild-type animals. Analysis of mutant somatic clones suggests a function in cell growth and proliferation, which is supported by the fact that cell proliferation is promoted by pit overexpression. Tagged-Pit, when transfected in S2 cells, localizes mainly to the nucleolus, pointing towards a possible role in ribosome biogenesis and, consequently, in protein biosynthesis. pit encodes a DEAD-box RNA helicase, a family of proteins involved in the control of RNA structure in many cellular processes and its closest homologue is a human DEAD-box RNA helicase, MrDb, whose corresponding gene transcription is directly activated by Myc-Max heterodimers (Grandori, C., Mac, J., Siebelt, F., Ayer, D. E. and Eisenman, R. N. (1996) EMBO J. 15, 4344–4357). The patterns of expression of d-myc and pit are superimposable. Ectopic expression of myc in the nervous system drives an ectopic expression of pit in this tissue indicating that in Drosophila as well, pit is a potential target of d-Myc. These results suggest that myc might promote cell proliferation by activating genes that are required in protein biosynthesis, thus linking cell growth and cell proliferation.

scholarly journals Light Stimuli and Circadian Clock Affect Neural Development in Drosophila melanogaster

2021 ◽  
Vol 9 ◽  
Author(s):  
Eleni Dapergola ◽  
Pamela Menegazzi ◽  
Thomas Raabe ◽  
Anna Hovhanyan
Keyword(s):  
Cell Growth ◽  
Circadian Clock ◽  
Neural Development ◽  
Ribosome Biogenesis ◽  
Neural Circuit ◽  
Protein Biosynthesis ◽  
Tor Signaling ◽  
Light Stimuli ◽  
And Function ◽  
Cell Growth And Proliferation

Endogenous clocks enable organisms to adapt cellular processes, physiology, and behavior to daily variation in environmental conditions. Metabolic processes in cyanobacteria to humans are under the influence of the circadian clock, and dysregulation of the circadian clock causes metabolic disorders. In mouse and Drosophila, the circadian clock influences translation of factors involved in ribosome biogenesis and synchronizes protein synthesis. Notably, nutrition signals are mediated by the insulin receptor/target of rapamycin (InR/TOR) pathways to regulate cellular metabolism and growth. However, the role of the circadian clock in Drosophila brain development and the potential impact of clock impairment on neural circuit formation and function is less understood. Here we demonstrate that changes in light stimuli or disruption of the molecular circadian clock cause a defect in neural stem cell growth and proliferation. Moreover, we show that disturbed cell growth and proliferation are accompanied by reduced nucleolar size indicative of impaired ribosomal biogenesis. Further, we define that light and clock independently affect the InR/TOR growth regulatory pathway due to the effect on regulators of protein biosynthesis. Altogether, these data suggest that alterations in InR/TOR signaling induced by changes in light conditions or disruption of the molecular clock have an impact on growth and proliferation properties of neural stem cells in the developing Drosophila brain.

A characterization of the effects of Dpp signaling on cell growth and proliferation in theDrosophilawing

Development ◽  
2002 ◽  
Vol 129 (4) ◽  
pp. 1003-1013 ◽  
Author(s):  
Cristina Martín-Castellanos ◽  
Bruce A. Edgar
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cell Cycle Progression ◽  
Ectopic Expression ◽  
Specific Inhibitor ◽  
Wing Disc ◽  
Cycle Progression ◽  
Cell Growth And Proliferation ◽  
Wing Cell

Cell proliferation and patterning must be coordinated for the development of properly proportioned organs. If the same molecules were to control both processes, such coordination would be ensured. Here we address this possibility in the Drosophila wing using the Dpp signaling pathway. Previous studies have shown that Dpp forms a gradient along the AP axis that patterns the wing, that Dpp receptors are autonomously required for wing cell proliferation, and that ectopic expression of either Dpp or an activated Dpp receptor, TkvQ253D, causes overgrowth. We extend these findings with a detailed analysis of the effects of Dpp signaling on wing cell growth and proliferation. Increasing Dpp signaling by expressing TkvQ253D accelerated wing cell growth and cell cycle progression in a coordinate and cell-autonomous manner. Conversely, autonomously inhibiting Dpp signaling using a pathway specific inhibitor, Dad, or a mutation in tkv, slowed wing cell growth and division, also in a coordinate fashion. Stimulation of cell cycle progression by TkvQ253D was blocked by the cell cycle inhibitor RBF, and required normal activity of the growth effector, PI3K. Among the known Dpp targets, vestigial was the only one tested that was required for TkvQ253D-induced growth. The growth response to altering Dpp signaling varied regionally and temporally in the wing disc, indicating that other patterned factors modify the response.

miR-449b-5p Inhibits Cell Proliferation and Migration of Breast Cancer via Targeting Flotillin-2

2020 ◽  
Vol 10 (8) ◽  
pp. 1094-1101
Author(s):  
Delin Wu ◽  
Xiaopeng Ma
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Breast Carcinoma ◽  
Critical Role ◽  
Ectopic Expression ◽  
Luciferase Reporter ◽  
Cell Growth And Migration ◽  
Cancer Pathogenesis ◽  
And Migration

Background: MicroRNAs (miRNAs) act as a critical role in cancer pathogenesis, while the potential of miR-449b-5p in breast carcinoma remains to be fully inquired. Therefore, we purposed to probe the mechanism governing miR-449b-5p in breast cancer. Methods: Reverse transcription-PCR (RTPCR) was adopted to examine miR-449b-5p expression level in breast carcinoma. The functional experiments were implemented to estimate the role of miR-449b-5p in cell growth and migration. The interplay of miR-449b-5p with FLOT2 was validated with luciferase reporter assay. Results: miR-449b-5p level was markedly lessened in the tissue samples and cell lines of breast carcinoma. Overexpression of miR-449b-5p contributed to suppression of cell growth and migration whereas induced apoptosis in SKBr-3 and MCF-7 cells. Moreover, luciferase reporter experiment suggested that FLOT2 had a negative correlation with miR-449b-5p expression. Functionally, ectopic expression of FLOT2 reversed repressive effects of miR-449b-5p mimic on malignant behaviors of breast carcinoma cells. Conclusion: miR-449b-5p hindered cell proliferation, migration and facilitated cell apoptosis of breast carcinoma through targeting FLOT2. Our findings may offer a potent target for the therapy of breast carcinoma.

scholarly journals Bystin in human cancer cells: intracellular localization and function in ribosome biogenesis

2007 ◽  
Vol 404 (3) ◽  
pp. 373-381 ◽  
Author(s):  
Masaya Miyoshi ◽  
Tetsuya Okajima ◽  
Tsukasa Matsuda ◽  
Michiko N. Fukuda ◽  
Daita Nadano
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Ribosomal Rna ◽  
Mammalian Cells ◽  
Ribosome Biogenesis ◽  
Human Cancer ◽  
Intracellular Localization ◽  
Promote Cell Proliferation ◽  
Human Cancer Cell Lines ◽  
Nucleolar Stress

Although bystin has been identified as a protein potentially involved in embryo implantation (a process unique to mammals) in humans, the bystin gene is evolutionarily conserved from yeast to humans. DNA microarray data indicates that bystin is overexpressed in human cancers, suggesting that it promotes cell growth. We undertook RT (reverse transcription)–PCR and immunoblotting, and confirmed that bystin mRNA and protein respectively are expressed in human cancer cell lines, including HeLa. Subcellular fractionation identified bystin protein as nuclear and cytoplasmic, and immunofluorescence showed that nuclear bystin localizes mainly in the nucleolus. Sucrose gradient ultracentrifugation of total cytoplasmic ribosomes revealed preferential association of bystin with the 40S subunit fractions. To analyse its function, bystin expression in cells was suppressed by RNAi (RNA interference). Pulse–chase analysis of ribosomal RNA processing suggested that bystin knockdown delays processing of 18S ribosomal RNA, a component of the 40S subunit. Furthermore, this knockdown significantly inhibited cell proliferation. Our findings suggest that bystin may promote cell proliferation by facilitating ribosome biogenesis, specifically in the production of the 40S subunit. Localization of bystin to the nucleolus, the site of ribosome biogenesis, was blocked by low concentrations of actinomycin D, a reagent that causes nucleolar stress. When bystin was transiently overexpressed in HeLa cells subjected to nucleolar stress, nuclear bystin was included in particles different from the nuclear stress granules induced by heat shock. In contrast, cytoplasmic bystin was barely affected by nucleolar stress. These results suggest that, while bystin may play multiple roles in mammalian cells, a conserved function is to facilitate ribosome biogenesis required for cell growth.

scholarly journals The DHX33 RNA Helicase Promotes mRNA Translation Initiation

2015 ◽  
Vol 35 (17) ◽  
pp. 2918-2931 ◽  
Author(s):  
Yandong Zhang ◽  
Jin You ◽  
Xingshun Wang ◽  
Jason Weber
Keyword(s):  
Translation Initiation ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Mrna Translation ◽  
Rna Helicase ◽  
Rna Helicases ◽  
80S Ribosome ◽  
Protein Levels ◽  
Cell Growth And Proliferation ◽  
Rna Complexes

DEAD/DEAH box RNA helicases play essential roles in numerous RNA metabolic processes, such as mRNA translation, pre-mRNA splicing, ribosome biogenesis, and double-stranded RNA sensing. Herein we show that a recently characterized DEAD/DEAH box RNA helicase, DHX33, promotes mRNA translation initiation. We isolated intact DHX33 protein/RNA complexes in cells and identified several ribosomal proteins, translation factors, and mRNAs. Reduction of DHX33 protein levels markedly reduced polyribosome formation and caused the global inhibition of mRNA translation that was rescued with wild-type DHX33 but not helicase-defective DHX33. Moreover, we observed an accumulation of mRNA complexes with the 80S ribosome in the absence of functional DHX33, consistent with a stalling in initiation, and DHX33 more preferentially promoted structured mRNA translation. We conclude that DHX33 functions to promote elongation-competent 80S ribosome assembly at the late stage of mRNA translation initiation. Our results reveal a newly recognized function of DHX33 in mRNA translation initiation, further solidifying its central role in promoting cell growth and proliferation.

scholarly journals Las1L Is a Nucleolar Protein Required for Cell Proliferation and Ribosome Biogenesis

2010 ◽  
Vol 30 (18) ◽  
pp. 4404-4414 ◽  
Author(s):  
Christopher D. Castle ◽  
Erica K. Cassimere ◽  
Jinho Lee ◽  
Catherine Denicourt
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Ribosome Biogenesis ◽  
Ribosomal Subunit ◽  
Nucleolar Protein ◽  
28S Rrna ◽  
Rrna Processing ◽  
Tumor Suppressor P53 ◽  
Growth Increase ◽  
Multistep Process

ABSTRACT Ribosome biogenesis is a highly regulated process ensuring that cell growth (increase in biomass) is coordinated with cell proliferation. The formation of eukaryotic ribosomes is a multistep process initiated by the transcription and processing of rRNA in the nucleolus. Concomitant with this, several preribosomal particles, which transiently associate with numerous nonribosomal factors before mature 60S and 40S subunits are formed and exported in the cytoplasm, are generated. Here we identify Las1L as a previously uncharacterized nucleolar protein required for ribosome biogenesis. Depletion of Las1L causes inhibition of cell proliferation characterized by a G1 arrest dependent on the tumor suppressor p53. Moreover, we demonstrate that Las1L is crucial for ribosome biogenesis and that depletion of Las1L leads to inhibition of rRNA processing and failure to synthesize the mature 28S rRNA. Taken together, our data demonstrate that Las1L is essential for cell proliferation and biogenesis of the 60S ribosomal subunit.

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