Growth and cell survival are unevenly impaired in<i>pixie</i>mutant wing discs

Coelho, Carmen M. A.; Kolevski, Benjamin; Bunn, Caroline; Walker, Cherryl D.; Dahanukar, Anupama; Leevers, Sally J.

doi:10.1242/dev.02148

Cited by 42 publications

(44 citation statements)

References 53 publications

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“…IR-induced changes in the expression of brk, puc, and hid are consistent with the production of aneuploid cells exhibiting the Minute phenotype, although these markers are not specific for aneuploid cells. Since haploinsufficiency of the widely distributed Minute genes is sufficient to induce apoptosis (Moreno et al 2002;Coelho et al 2005) and induction of spontaneous apoptosis in Minute heterozygous animals does not require p53 (L. M. McNamee, unpublished results), this mechanism should eventually be activated in aneuploid cells induced by IR. While Minute genes represent the primary source of loci that are haploinsufficient for normal growth (Lindsley et al 1972;Marygold et al 2007), it is also possible that the cumulative effect of reduced dosage of many genes in aneuploid cells disrupts normal gene expression and cell survival.…”

Section: Discussionmentioning

confidence: 99%

p53-Independent Apoptosis Limits DNA Damage-Induced Aneuploidy

2009

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DNA damage or unprotected telomeres can trigger apoptosis via signaling pathways that directly sense abnormal DNA structures and activate the p53 transcription factor. We describe a p53-independent mechanism that acts in parallel to the canonical DNA damage response pathway in Drosophila to induce apoptosis after exposure to ionizing radiation. Following recovery from damage-induced cell cycle arrest, p53 mutant cells activate the JNK pathway and expression of the pro-apoptotic gene hid. Mutations in grp, a cell cycle checkpoint gene, and puc, a negative regulator of the JNK pathway, sensitize p53 mutant cells to ionizing radiation (IR)-induced apoptosis. Induction of chromosome aberrations by DNA damage generates cells with segmental aneuploidy and heterozygous for mutations in ribosomal protein genes. p53-independent apoptosis limits the formation of these aneuploid cells following DNA damage. We propose that reduced copy number of haploinsufficient genes following chromosome damage activates apoptosis and helps maintain genomic integrity.

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Section: Discussionmentioning

confidence: 99%

p53-Independent Apoptosis Limits DNA Damage-Induced Aneuploidy

2009

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“…87 The mechanism of ABCE1 involvement in histone biosynthesis remains to be established, but presumably could be related to its well-recognized function in translation. Since ABCE1 depletion has been previously shown to inhibit total translation in several organisms, 10,16,17 we decided to investigate whether insufficient histone synthesis in ABCE1-downregulated cells could be a consequence of general translation deficiency. Consistently with the previous reports, the total protein synthesis in ABCE1-depleted cells was significantly impaired (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The cell cycle defect in ABCE1-depleted cells occurs before a dramatic decrease of total translation Since ABCE1 is recognized as an essential translation factor in several organisms, 10,14,17 we considered it plausible that ABCE1 could be implicated in histone synthesis via its general function in translation. We therefore decided to examine the status of total protein synthesis in ABCE1-downregulated cells.…”

Section: Abce1 Downregulation Impairs Cell Proliferation and Cell Cycmentioning

confidence: 99%

“…5 In all studied organisms, loss in ABCE1 function appears to be lethal or causing severe defects in growth and development. [6][7][8][9][10] Human ABCE1 was first characterized as an inhibitor of RNase L, a latent endoribonuclease functioning on the interferon-dependent antiviral 2-5A pathway. 11 Besides antiviral activity, this pathway plays a more general role in regulation of cellular RNA expression and turnover.…”

Section: Introductionmentioning

confidence: 99%

“…[15][16][17][18] Consistently, ABCE1 depletion results in reduced polysome content and global translation in yeast, mammalian and Drosophila cells. 10,14,[16][17][18] ABCE1 is also involved in translation termination through interaction with release factors eRF1 and eRF3, occupying the GTPase center. 19,20 Interestingly, its function in termination could be shared with RNase L that might balance mRNA turnover and translation.…”

Section: Introductionmentioning

confidence: 99%

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ABCE1 is essential for S phase progression in human cells

et al. 2016

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ABCE1 is a highly conserved protein universally present in eukaryotes and archaea, which is crucial for the viability of different organisms. First identified as RNase L inhibitor, ABCE1 is currently recognized as an essential translation factor involved in several stages of eukaryotic translation and ribosome biogenesis. The nature of vital functions of ABCE1, however, remains unexplained. Here, we study the role of ABCE1 in human cell proliferation and its possible connection to translation. We show that ABCE1 depletion by siRNA results in a decreased rate of cell growth due to accumulation of cells in S phase, which is accompanied by inefficient DNA synthesis and reduced histone mRNA and protein levels. We infer that in addition to the role in general translation, ABCE1 is involved in histone biosynthesis and DNA replication and therefore is essential for normal S phase progression. In addition, we analyze whether ABCE1 is implicated in transcript-specific translation via its association with the eIF3 complex subunits known to control the synthesis of cell proliferation-related proteins. The expression levels of a few such targets regulated by eIF3A, however, were not consistently affected by ABCE1 depletion.

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