Abstract
SummaryThe cell cycle is coordinated with differentiation during animal development. Here we report a cell-cycle-independent developmental role for a master cell-cycle regulator, the anaphase-promoting complex or cyclosome (APC/C), in the regulation of cell fate through modulation of Wingless (Wg) signaling. The APC/C controls both cell-cycle progression and postmitotic processes through ubiquitin-dependent proteolysis. Through an RNAi screen in the developing Drosophila eye, we found that partial APC/C inactivation severely inhibits retinal differentiation independently of cell-cycle defects. The differentiation inhibition coincides with hyperactivation of Wg signaling caused by the accumulation of a Wg modulator, Drosophila Nek2 (dNek2). The APC/C degrades dNek2 upon synchronous G1 arrest prior to differentiation, which allows retinal differentiation through local suppression of Wg signaling. We also provide evidence that decapentaplegic signaling may posttranslationally regulate this APC/C function. Thus, the APC/C coordinates cell-fate determination with the cell cycle through the modulation of developmental signaling pathways.
Highlights
During development of multicellular organisms, the cell cycle is highly coordinated with differentiation
By performing an RNAi screen in the developing Drosophila eye, we found that partial anaphase-promoting complex or cyclosome (APC/C) inactivation strongly inhibits retinal differentiation
Our study demonstrates that the APC/C coordinates retinal differentiation by modulating Wg signaling through Drosophila Nek2 (dNek2) degradation
Summary
During development of multicellular organisms, the cell cycle is highly coordinated with differentiation. The coordination between the cell cycle and differentiation must be strictly regulated to form and maintain functional tissues and organs. Uncoupling of this coordination may lead to tumorigenesis, tissue degeneration, and aging. To facilitate this coordination, a set of the cell-cycle regulators possess the ability to regulate differentiation processes. A set of the cell-cycle regulators possess the ability to regulate differentiation processes Among such regulators is the anaphase-promoting complex or cyclosome (APC/C), an evolutionarily conserved ubiquitin ligase complex that controls cell-cycle progression via ubiquitin-mediated proteolysis (Pines, 2011). Non-cell-cycle functions of the APC/C and the underlying mechanisms remain unexplored
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