Drosophila homologues of the transcriptional coactivation complex subunits TRAP240 and TRAP230 are required for identical processes in eye-antennal disc development

Development ◽  
2001 ◽  
Vol 128 (4) ◽  
pp. 603-615 ◽  
Author(s):  
J. Treisman
Keyword(s):  
Cell Proliferation ◽  
Notch Signaling ◽  
Hedgehog Signaling ◽  
Blind Spot ◽  
Mediator Complex ◽  
Eye Disc ◽  
Disc Cells ◽  
Inappropriate Expression ◽  
Mutant Cells ◽  
Antennal Disc

We have identified mutations in two genes, blind spot and kohtalo, that encode Drosophila homologues of human TRAP240 and TRAP230, components of a large transcriptional coactivation complex homologous to the yeast Mediator complex. Loss of either blind spot or kohtalo has identical effects on the development of the eye-antennal disc. Eye disc cells mutant for either gene can express decapentaplegic and atonal in response to Hedgehog signaling, but they maintain inappropriate expression of these genes and fail to differentiate further. Mutant cells in the antennal disc lose expression of Distal-less and misexpress eyeless, suggesting a partial transformation towards the eye fate. blind spot and kohtalo are not required for cell proliferation or survival, and their absence cannot be rescued by activation of the Hedgehog or Notch signaling pathways. These novel and specific phenotypes suggest that TRAP240 and TRAP230 act in concert to mediate an unknown developmental signal or a combination of signals.

The role of RBF in developmentally regulated cell proliferation in the eye disc and in Cyclin D/Cdk4 induced cellular growth

Development ◽  
2002 ◽  
Vol 129 (6) ◽  
pp. 1345-1356 ◽  
Author(s):  
Shijie Xin ◽  
Li Weng ◽  
Jinhua Xu ◽  
Wei Du
Keyword(s):  
Cell Proliferation ◽  
Eye Development ◽  
S Phase ◽  
Cellular Growth ◽  
Mutant Form ◽  
Cyclin D ◽  
Mitotic Wave ◽  
Eye Disc ◽  
Disc Cells

During Drosophila eye development, cell proliferation is coordinated with differentiation. Immediately posterior to the morphogenetic furrow, cells enter a synchronous round of S phase called second mitotic wave. We have examined the role of RBF, the Drosophila RB family homolog, in cell cycle progression in the second mitotic wave. RBF-280, a mutant form of RBF that has four putative cdk phosphorylation sites mutated, can no longer be regulated by Cyclin D or Cyclin E. Expression of RBF-280 in the developing eye revealed that RBF-280 does not inhibit G1/S transition in the second mitotic wave, rather it delays the completion of S phase and leads to abnormal eye development. These observations suggest that RB/E2F control the rate of S-phase progression instead of G1/S transition in the second mitotic wave. Characterization of the role of RBF in Cyclin D/Cdk4-mediated cellular growth showed that RBF-280 blocks Cyclin D/Cdk4 induced cellular growth in the proliferating wing disc cells but not in the non-dividing eye disc cells. By contrast, RBF-280 does not block activated Ras-induced cellular growth. These results suggest that the ability of Cyclin D/Cdk4 to drive growth in the proliferating wing cells is distinct from that in the none-dividing eye cells or the ability of activated Ras to induce growth, and that RBF may have a role in regulating growth in the proliferating wing discs.

Expanded: a gene involved in the control of cell proliferation in imaginal discs

Development ◽  
1993 ◽  
Vol 118 (4) ◽  
pp. 1291-1301 ◽  
Author(s):  
M. Boedigheimer ◽  
A. Laughon
Keyword(s):  
Cell Proliferation ◽  
Protein Interactions ◽  
Essential Gene ◽  
Spontaneous Mutation ◽  
Growth Control ◽  
Imaginal Discs ◽  
Apical Surface ◽  
Protein Protein Interactions ◽  
Acid Protein ◽  
Disc Cells

The expanded gene was first identified by a spontaneous mutation that causes broad wings. We have identified an enhancer-trap insertion within expanded and used it to generate additional mutations, including one null allele. expanded is an essential gene, necessary for proper growth control of imaginal discs and, when mutant, causes either hyperplasia or degeneration depending on the disc. Wing overgrowth in expanded hypermorphs is limited to specific regions along the anterior-posterior and dorsal-ventral axis. expanded encodes a novel 1429 amino acid protein that is localized to the apical surface of disc cells and contains three potential SH3-binding sites. Together, these observations suggest that the Expanded protein engages in protein-protein interactions regulating cell proliferation in discs.

Cell proliferation control by Notch signaling in Drosophila development

Development ◽  
1998 ◽  
Vol 125 (11) ◽  
pp. 2031-2040 ◽  
Author(s):  
M.J. Go ◽  
D.S. Eastman ◽  
S. Artavanis-Tsakonas
Keyword(s):  
Cell Proliferation ◽  
Notch Signaling ◽  
Imaginal Disc ◽  
Synergistic Effects ◽  
Wing Disc ◽  
Notch Receptor ◽  
Simple Consequence ◽  
Undifferentiated Cells ◽  
Cell Proliferation Control ◽  
Stimulation Of

The Notch receptor mediates cell interactions controlling the developmental fate of a broad spectrum of undifferentiated cells. By modulating Notch signaling in specific precursor cells during Drosophila imaginal disc development, we demonstrate that Notch activity can influence cell proliferation. The activation of the Notch receptor in the wing disc induces the expression of the wing margin patterning genes vestigial and wingless, and strong mitotic activity. However, the effect of Notch signaling on cell proliferation is not the simple consequence of the upregulation of either vestigial or wingless. Vestigial and Wingless, on the contrary, display synergistic effects with Notch signaling, resulting in the stimulation of cell proliferation in imaginal discs.

Smoothened-independent activation of hedgehog signaling by rearranged during transfection promotes neuroblastoma cell proliferation and tumor growth

2016 ◽  
Vol 1860 (9) ◽  
pp. 1961-1972 ◽  
Author(s):  
Hongfeng Ruan ◽  
Huan Luo ◽  
Jirong Wang ◽  
Xing Ji ◽  
Zhongmiao Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Growth ◽  
Hedgehog Signaling ◽  
Neuroblastoma Cell

scholarly journals dE2F2-Independent Rescue of Proliferation in Cells Lacking an Activator dE2F1

2007 ◽  
Vol 27 (24) ◽  
pp. 8561-8570 ◽  
Author(s):  
Aaron M. Ambrus ◽  
Brandon N. Nicolay ◽  
Vanya I. Rasheva ◽  
Richard J. Suckling ◽  
Maxim V. Frolov
Keyword(s):  
Cell Cycle ◽  
Morphogenetic Furrow ◽  
Independent Manner ◽  
Dead Box ◽  
Cycle Arrest ◽  
Eye Disc ◽  
Severe Reduction ◽  
Functional Inactivation ◽  
Mutant Cells ◽  
Dependent Mechanism

ABSTRACT In Drosophila melanogaster, the loss of activator de2f1 leads to a severe reduction in cell proliferation and repression of E2F targets. To date, the only known way to rescue the proliferation block in de2f1 mutants was through the inactivation of dE2F2. This suggests that dE2F2 provides a major contribution to the de2f1 mutant phenotype. Here, we report that in mosaic animals, in addition to de2f2, the loss of a DEAD box protein Belle (Bel) also rescues proliferation of de2f1 mutant cells. Surprisingly, the rescue occurs in a dE2F2-independent manner since the loss of Bel does not relieve dE2F2-mediated repression. In the eye disc, bel mutant cells fail to undergo a G1 arrest in the morphogenetic furrow, delay photoreceptor recruitment and differentiation, and show a reduction of the transcription factor Ci155. The down-regulation of Ci155 is important since it is sufficient to partially rescue proliferation of de2f1 mutant cells. Thus, mutation of bel relieves the dE2F2-mediated cell cycle arrest in de2f1 mutant cells through a novel Ci155-dependent mechanism without functional inactivation of the dE2F2 repressor.

scholarly journals Control of Cell Proliferation in the Drosophila Eye by Notch Signaling

2005 ◽  
Vol 8 (4) ◽  
pp. 529-539 ◽  
Author(s):  
Antonio Baonza ◽  
Matthew Freeman
Keyword(s):  
Cell Proliferation ◽  
Notch Signaling ◽  
Drosophila Eye

scholarly journals PIK3CAmutant tumors depend on oxoglutarate dehydrogenase

2017 ◽  
Vol 114 (17) ◽  
pp. E3434-E3443 ◽  
Author(s):  
Nina Ilic ◽  
Kıvanç Birsoy ◽  
Andrew J. Aguirre ◽  
Nora Kory ◽  
Michael E. Pacold ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glucose Metabolism ◽  
Cancer Cell ◽  
Mutant Cell ◽  
Tca Cycle ◽  
Loss Of Function ◽  
Cycle Enzyme ◽  
Oxoglutarate Dehydrogenase ◽  
Mutant Cells ◽  
Malate Aspartate Shuttle

OncogenicPIK3CAmutations are found in a significant fraction of human cancers, but therapeutic inhibition of PI3K has only shown limited success in clinical trials. To understand how mutant PIK3CA contributes to cancer cell proliferation, we used genome scale loss-of-function screening in a large number of genomically annotated cancer cell lines. As expected, we found thatPIK3CAmutant cancer cells requirePIK3CAbut also require the expression of the TCA cycle enzyme 2-oxoglutarate dehydrogenase (OGDH). To understand the relationship between oncogenic PIK3CA and OGDH function, we interrogated metabolic requirements and found an increased reliance on glucose metabolism to sustainPIK3CAmutant cell proliferation. Functional metabolic studies revealed that OGDH suppression increased levels of the metabolite 2-oxoglutarate (2OG). We found that this increase in 2OG levels, either by OGDH suppression or exogenous 2OG treatment, resulted in aspartate depletion that was specifically manifested as auxotrophy withinPIK3CAmutant cells. Reduced levels of aspartate deregulated the malate–aspartate shuttle, which is important for cytoplasmic NAD+regeneration that sustains rapid glucose breakdown through glycolysis. Consequently, becausePIK3CAmutant cells exhibit a profound reliance on glucose metabolism, malate–aspartate shuttle deregulation leads to a specific proliferative block due to the inability to maintain NAD+/NADH homeostasis. Together these observations define a precise metabolic vulnerability imposed by a recurrently mutated oncogene.

Triptolide suppresses pancreatic cancer cell proliferation by inhibiting hedgehog signaling pathway activity

2019 ◽  
Vol 62 (10) ◽  
pp. 1409-1412 ◽  
Author(s):  
Juanjuan Feng ◽  
Mingjin Rao ◽  
Man Wang ◽  
Lin Liang ◽  
Zhi Chen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Hedgehog Signaling ◽  
Pancreatic Cancer Cell ◽  
Hedgehog Signaling Pathway ◽  
Cancer Cell Proliferation ◽  
Pathway Activity
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