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Citation
Mandal, S., Freije, W.A., Guptan, P., Banerjee, U. (2010). Metabolic control of G1-S transition: cyclin E degradation by p53-induced activation of the ubiquitin-proteasome system.  J. Cell Biol. 188(4): 473--479.
FlyBase ID
FBrf0210063
Publication Type
Research paper
Abstract

Cell cycle progression is precisely regulated by diverse extrinsic and intrinsic cellular factors. Previous genetic analysis in Drosophila melanogaster has shown that disruption of the mitochondrial electron transport chain activates a G1-S checkpoint as a result of a control of cyclin E by p53. This regulation does not involve activation of the p27 homologue dacapo in flies. We demonstrate that regulation of cyclin E is not at the level of transcription or translation. Rather, attenuated mitochondrial activity leads to transcriptional upregulation of the F-box protein archipelago, the Fbxw7 homologue in flies. We establish that archipelago and the proteasomal machinery contribute to degradation of cyclin E in response to mitochondrial dysfunction. Our work provides in vivo genetic evidence for p53-mediated integration of metabolic stress signals, which modulate the activity of the ubiquitin-proteasome system to degrade cyclin E protein and thereby impose cell cycle arrest.

PubMed ID
PubMed Central ID
PMC2828916 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Cell Biol.
    Title
    Journal of Cell Biology
    Publication Year
    1966-
    ISBN/ISSN
    0021-9525
    Data From Reference
    Alleles (6)
    Genes (8)