Drosophila Low Temperature Viability Protein 1 (LTV1) Is Required for Ribosome Biogenesis and Cell Growth Downstream of Drosophila Myc (dMyc)

Kim, Won‐Ho; Kim, Hag Dong; Jung, Youjin; Kim, Joon; Chung, Jongkyeong

doi:10.1074/jbc.m114.607036

Cited by 9 publications

(8 citation statements)

References 43 publications

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“…Given the ribosomal nature of RPL10, the reduced translation of p65 and IKKγ might attribute to the dysfunction of ribosomal biogenesis. So far, the importance of ribosome function and translational control in tumorigenesis has been underscored although several oncogenes, such as Myc [ 25 ], and tumor suppressor genes, such as PTEN [ 26 ] and p53 [ 27 ], have been linked to direct regulation of ribosome production and protein translation. In prostate cancer patients, reduced expression of RPL10 has been suggested to associate with early development of the cancer; however, high expression of RPL10 at later stages of cancer development could drive forward to a more aggressive phenotype [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Cooperative down-regulation of ribosomal protein L10 and NF-κB signaling pathway is responsible for the anti-proliferative effects by DMAPT in pancreatic cancer cells

et al. 2017

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Dimethylaminoparthenolide (DMAPT), a water-soluble analogue of natural product parthenolide, possesses anti-inflammatory and anti-tumor activities. Despite that the anti-inflammatory mechanism of DMAPT has been well studied, specific target(s) for DMPAT and its anti-tumor mechanism remain poorly understood. In this study, to assess the anti-proliferative effects of DMAPT in pancreatic cancer cell lines and exploit its anti-tumor mechanism, serial affinity chromatograph was implemented to probe potential targets for DMAPT, revealing that ribosomal protein L10 (RPL10) is a specific binding protein of DMAPT in PANC-1 cells. DMAPT could decrease the expression of RPL10 accompanying its anti-proliferative effects. Mechanistically, in both PANC-1 cells and MiaPaca-2 cells, reduced expression of RPL10 triggered by DMAPT binding decreased the expression of either p65 or IKKγ through the direct binding between RPL10 and p65 or IKKγ. Together, the present study strongly implies that RPL10 is a novel target with therapeutic potential for the treatment of pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Cooperative down-regulation of ribosomal protein L10 and NF-κB signaling pathway is responsible for the anti-proliferative effects by DMAPT in pancreatic cancer cells

et al. 2017

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“…Drosophila S2 Cell Culture and dsRNA Bathing Drosophila melanogaster S2 cells were maintained in Shields and Sang M3 media (Sigma, S8398) supplemented with 10% FBS and Penicillin-Streptomycin. Double-stranded RNA (dsRNA) was synthesized and treated as previously described (Kim et al, 2015). For amino acid-starvation, S2 cells were washed once in PBS, and then incubated in Schneider media without amino acids (US Biological, S0100-01) for 1 hour.…”

Section: Star+methodsmentioning

confidence: 99%

Spatial Activation of TORC1 Is Regulated by Hedgehog and E2F1 Signaling in the Drosophila Eye

et al. 2017

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Target of rapamycin complex 1 (TORC1) regulates cell growth in response to nutrients and growth factors. Although TORC1 signaling has been thoroughly studied at the cellular level, the regulation of TORC1 in multicellular tissues and organs has remained elusive. Here we found that TORC1 is selectively activated in the second mitotic wave (SMW), the terminal synchronous cell division, of the developing Drosophila eye. We demonstrated that Hedgehog (Hh) signaling regulates TORC1 through E2F1 and the cyclin D/Cdk4 complex in the SMW, and this regulation is independent from insulin and amino acid signaling pathways. TORC1 is necessary for the proper G1/S transition of the cells, and the activation of TORC1 rescues the cell-cycle defect of Hh signaling-deficient cells in the SMW. Based on this evolutionarily conserved regulation of TORC1 by Hh signaling, we propose that Hh-dependent developmental signaling pathways spatially regulate TORC1 activity in multicellular organisms.

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“…Drosophila S2-DRSC cells were cultured and dsRNA bathing was conducted as described previously (57). For silencing mRNA expression of MCU and IP 3 R, dsRNA was synthesized and bathed.…”

Section: Drosophila S2 Cell Culture and Dsrna Bathingmentioning

confidence: 99%

Mitochondrial calcium uniporter in Drosophila transfers calcium between the endoplasmic reticulum and mitochondria in oxidative stress-induced cell death

Choi

Quan

Bang

et al. 2017

Journal of Biological Chemistry

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Mitochondrial calcium plays critical roles in diverse cellular processes ranging from energy metabolism to cell death. Previous studies have demonstrated that mitochondrial calcium uptake is mainly mediated by the mitochondrial calcium uniporter (MCU) complex. However, the roles of the MCU complex in calcium transport, signaling, and dysregulation by oxidative stress still remain unclear. Here, we confirmed that MCU contains evolutionarily conserved structures and requires essential MCU regulator (EMRE) for its calcium channel activities. We generated MCU loss-of-function mutants, which lacked mitochondrial calcium uptake in response to caffeine stimulation. Basal metabolic activities were not significantly affected in these MCU mutants, as observed in examinations of body weight, food intake, body sugar level, and starvation-induced autophagy. However, oxidative stress-induced increases in mitochondrial calcium, mitochondrial membrane potential depolarization, and cell death were prevented in these mutants. We also found that inositol 1,4,5-trisphosphate receptor genetically interacts with MCU and effectively modulates mitochondrial calcium uptake upon oxidative stress. Taken together, these results support the idea that MCU is responsible for endoplasmic reticulum-to-mitochondrial calcium transfer and for cell death due to mitochondrial dysfunction under oxidative stress.

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Drosophila Low Temperature Viability Protein 1 (LTV1) Is Required for Ribosome Biogenesis and Cell Growth Downstream of Drosophila Myc (dMyc)

Cited by 9 publications

References 43 publications

Cooperative down-regulation of ribosomal protein L10 and NF-κB signaling pathway is responsible for the anti-proliferative effects by DMAPT in pancreatic cancer cells

Cooperative down-regulation of ribosomal protein L10 and NF-κB signaling pathway is responsible for the anti-proliferative effects by DMAPT in pancreatic cancer cells

Spatial Activation of TORC1 Is Regulated by Hedgehog and E2F1 Signaling in the Drosophila Eye

Mitochondrial calcium uniporter in Drosophila transfers calcium between the endoplasmic reticulum and mitochondria in oxidative stress-induced cell death

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