Roles of C/EBP class bZip proteins in the growth and cell competition of Rp (‘Minute’) mutants in Drosophila

eLife, Год журнала: 2019, Номер 9

Опубликована: Дек. 24, 2019

Reduced copy number of ribosomal protein (Rp) genes adversely affects both flies and mammals. Xrp1 encodes a reportedly Drosophila-specific AT-hook, bZIP responsible for many the effects including elimination Rp mutant cells by competition with wild type cells. Irbp18, an evolutionarily conserved gene, heterodimerizes another bZip protein, dATF4. We show that Irbp18 is required Xrp1, whereas dATF4 does not share same phenotype, indicating Xrp1/Irbp18 complex active in cells, independently other complexes Irbp18. transcripts proteins are upregulated auto-regulatory expression depends on DNA binding domains necessary cell competition. beyond Drosophila, although under positive selection rapid evolution, at least one human can similarly affect Drosophila development.

Язык: Английский

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A p53-dependent translational program directs tissue-selective phenotypes in a model of ribosomopathies

Developmental Cell, Год журнала: 2021, Номер 56(14), С. 2089 - 2102.e11

Опубликована: Июль 1, 2021

Язык: Английский

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Cell competition removes segmental aneuploid cells from Drosophila imaginal disc-derived tissues based on ribosomal protein gene dose

eLife, Год журнала: 2021, Номер 10

Опубликована: Апрель 13, 2021

Aneuploidy causes birth defects and miscarriages, occurs in nearly all cancers is a hallmark of aging. Individual aneuploid cells can be eliminated from developing tissues by unknown mechanisms. Cells with ribosomal protein (Rp) gene mutations are also eliminated, cell competition normal cells. Because Rp genes spread across the genome, their copy number potential marker for aneuploidy. We found that elimination imaginal disc irradiation-induced genome damage often required genes. Segmentally derived targeted chromosome excisions were RpS12-Xrp1 pathway if they differed neighboring dose, whereas doses eIF2γ survived differentiated adult tissues. Thus, competition, triggered differences dose between cells, significant mechanism somatic likely to contribute preventing cancer.Aneuploid emerge when cellular division goes awry ends up wrong chromosomes, tiny genetic structures carrying instructions control life’s processes. lead fatal conditions during development, cancer an organism. A safety may exist helps body detect remove these Yet, exactly this happens still poorly understood: particular, it unclear how manage ‘count’ chromosomes. One way could do so through ribosomes, molecular ‘factories’ create building blocks life. In cell, every carries code proteins (known as Rps) forming ribosomes. will alter genes, turn amount type Rps produces, ribosomes act ‘readout’ Ji et al set out test theory fruit flies. The first experiment used manipulation technique called site-specific recombination parts chromosomes eye wing. which retained survived, while those missing some usually died – but only surrounding normal. situation, healthy damaged neighbours process known competition. second experiment, using radiation alternative method damaging gave similar results. work al. reveals eliminate potentially before cause harm. If same applies humans, boosting may, one day, combat diseases like cancer.

Язык: Английский

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The transcription factor Xrp1 orchestrates both reduced translation and cell competition upon defective ribosome assembly or function

eLife, Год журнала: 2022, Номер 11

Опубликована: Фев. 18, 2022

Ribosomal Protein ( Rp ) gene haploinsufficiency affects translation rate, can lead to protein aggregation, and causes cell elimination by competition with wild type cells in mosaic tissues. We find that the modest changes ribosomal subunit levels observed were insufficient for these effects, which all depended on AT-hook, bZip domain Xrp1. Xrp1 reduced global through PERK-dependent phosphorylation of eIF2α. eIF2α was itself sufficient enable otherwise cells, but expression, not as downstream effector Unexpectedly, many other defects reducing ribosome biogenesis or function (depletion TAF1B, eIF2, eIF4G, eIF6, eEF2, eEF1α1, eIF5A), also increased enabled competition. This expression induced depletions. In absence Xrp1, differences between themselves trigger is shown here be a sequence-specific transcription factor regulates transposable elements well single-copy genes. Thus, master regulator triggers multiple consequences stresses key instigator

Язык: Английский

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Collective cell migration relies on PPP1R15-mediated regulation of the endoplasmic reticulum stress response

Current Biology, Год журнала: 2024, Номер 34(7), С. 1390 - 1402.e4

Опубликована: Фев. 29, 2024

Язык: Английский

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