BRUCE EDGAR

..TOR activity is regulated by nutritional cues, suggesting that Rheb might either control, or respond to, nutrient availability...

..This conserved signaling pathway contains several tumor-suppressor genes and regulates the contact inhibition of proliferation in cultured cells...

..However, we still understand little about how size is actually sensed, or how organ-intrinsic size controls interface with whole-body physiology...

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..We infer that dE2F and RBF function specifically in cell cycle control, and that cell cycle acceleration is insufficient to stimulate growth. Variations in dE2F activity could be used to coordinate cell division with growth...

..Interaction tests with a Drosophila Rb homolog, RBF, indicate that CycD-Cdk4 can counteract the cell cycle suppressive effects of RBF, but that its growth promoting activity is mediated at least in part via other targets...

..Our results indicate that dMyc links patterning signals to cell division by regulating primary targets involved in cellular growth and metabolism...

..We propose that Ras primarily promotes growth and that growth is coupled to G1/S progression via cyclin E. Interestingly, upregulation of growth by Ras did not deregulate G2/M progression or a developmentally regulated cell cycle exit...

..The dual control mechanism used by imaginal disc cells allows integration of diverse inputs which operate in both cell specification and cell metabolism...

..Unlike timing or counting mechanisms, this mechanism can compensate for losses or additions of nuclei by altering the timing and number of the maternal cycles and thus will always generate the correct cell density at the MZT...

..Down-regulation of a cyclin specific to the G1 phase of the cell cycle, cyclin E, terminates the initial period of cell proliferation in developing Drosophila embryos...

..These results demonstrate a fundamental difference in the control of cell cycle activation and maintenance in these two cell types, and imply the existence of a novel mitogen generated by the larval fat body in response to nutrition...

..We suggest that, during evolution, cell-type-specific control elements were acquired by a simple growth-regulated promoter as a means of coordinating cell division with developmental processes, particularly neurogenesis...

..Notch activity creates a third domain by preventing arrest at G2 in wg-expressing cells, resulting in their arrest in G1...

..Recent work has identified several mechanisms which couple cell division to growth. Different mechanisms are used at different times during development to coordinate growth, cell division, and patterning...

..The isolation of non-cell-autonomous larval growth-defective mutants suggests that specialized organs coordinate growth throughout the animal and provides new tools for studies of organismal growth regulation...

..Overexpression of the wild-type gene causes cell death and disrupts the normal development of adult structures. The ppan gene family appears to have an essential and evolutionarily conserved role in cell growth...

..We further show that the dMyc antagonist dMnt inhibits rRNA transcription in the wing disc. Our results support the view that the Myc/Max/Mad network influences transcription on a global scale...

..These studies have also suggested how growth and cell-cycle progression may be coupled...

..Furthermore, Hif-1 prolyl hydroxylase (Hph) is required for both complexes to drive growth. Our data suggest that the growth-specific function of CycD/Cdk4 is conserved from arthropods to mammals...

..In other cell types, however (e.g., wing epithelial cells), unknown mechanisms inhibit E2F and Cyclin/Cdk activity in parallel to enforce permanent cell cycle exit upon terminal differentiation...

..A null mutation in CSN subunit 4 and hypomorphic mutations in csn5 lead to more severe defects than seen in the csn5-null mutants strain, suggesting that CSN5 carries only some of the CSN function...

..Although poorly characterized in mammals, several components of the Hippo pathway seem to be tumour suppressors in humans...

..This review focuses on describing recent advances in deciphering how terminal differentiation and exit from the cell cycle are coordinated...

..Stimulation of rRNA synthesis by TIF-IA may therefore provide a feed-forward mechanism to coregulate the levels of other ribosome components...

..The TEAD/TEF factor Scalloped (Sd) has been identified as the first known transcription factor to partner with Yki as a downstream target of Hpo signaling...

..In addition, we present protocols for performing flow cytometry on fixed or live-cultured Drosophila S2 cells...

..Our results demonstrate that dMnt is a transcriptional repressor that regulates D. melanogaster body size...

..Furthermore, brat overexpressing cells contain less ribosomal RNA than control cells. These results suggest that the tumorous phenotype of brat mutants may be due to excess cell growth and ribosome synthesis...

..Hence we surmise that an essential function of insulin/PI3K signaling in Drosophila is to coordinate cellular metabolism with nutritional conditions...

..The growth response to altering Dpp signaling varied regionally and temporally in the wing disc, indicating that other patterned factors modify the response...

..Several physiological repercussions of altering cell size have been identified...

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..These results suggest that a fundamental aspect of Max network function involves widespread binding and regulation of gene expression...

..Now, evidence has been provided that such checkpoints probably do not exist in mammalian cells. These findings highlight an important difference between how yeast and animal cells proliferate in response to extracellular cues...

..Levels of rheb mRNA are rapidly induced in response to protein starvation, and overexpressed Rheb can drive cell growth in starved animals, suggesting a role for Rheb in the nutritional control of cell growth...

..Point mutations in the GAP domain of Tsc2 disrupted its ability to regulate Rheb without affecting the ability of Tsc2 to form a complex with Tsc1. Our studies identify Rheb as a molecular target of the TSC tumour suppressors...

..Our data suggest that Hph, in addition to its function in hypoxic response, is a regulator of cellular growth and that it is a key mediator for CycD/Cdk4...

..g., by ectopic Dacapo, dWee1, dMyc, or Rheb). Without dE2F1, the compensatory mechanism fails, and treatments that alter Cdk activity cause aberrant cell cycle timing and cell death...

..Our results indicate that larval growth and endoreplication are coupled processes that, although linked to cell cycle control mechanisms, are regulated by dMyc and dMnt...

..The reduced cellular and organismal growth rates observed in both mutants indicate that Cyclin D-Cdk4 acts as a growth driver...

..Both functions depend on mRpL12 dosage, suggesting that CycD/Cdk4, mRpL12 and Hph function together in a common pathway that controls cell growth via affecting mitochondrial activity...

..Ras, therefore, regulates both the transcriptional responses necessary for vein cell identity, and the cell adhesive changes that determine vein and intervein cell morphology...

..CSN8 is present exclusively as part of the CSN holo-complex, and lack of CSN8 in the mutants leads to CSN instability. Consistent with this, Cullin deneddylation is impaired in the csn8(null) mutants...

..In addition, the growth effects of dMyc in larval wing imaginal discs require de novo rRNA synthesis. We suggest that during animal development, the control of rRNA synthesis and ribosome biogenesis is an essential Myc function...

..It has relevance to medical conditions involving cell and tissue growth including cancer diagnosis and therapy, regeneration, wound healing, diabetes and other metabolic diseases. ..

..Such genes are expected to be effectors of deregulated cell growth in tuberous sclerosis, and as such constitute potential targets for diagnosis and treatment of the disease. ..

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..Some of the identified genes could be useful targets for cancer diagnosis or anti-cancer chemotherapeutics. ..

..Such genes are expected to be effectors of deregulated cell growth in tuberous sclerosis, and as such constitute potential targets for diagnosis and treatment of the disease. ..

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..Thus we expect this work to be highly relevant to growth control in human development, tissue homeostasis, wound healing, and regeneration. ..

..The identification of growth regulatory genes in flies should also provide entry points for studies of cell growth control in humans during both normal and neoplastic development. ..

..Such genes are expected to be effectors of deregulated cell growth in tuberous sclerosis, and as such constitute potential targets for diagnosis and treatment of the disease. ..