title: Transcriptional networks controlling the cell cycle.
abstract: In this work, we map the transcriptional targets of 107 previously identified Drosophila genes whose loss caused the strongest cell-cycle phenotypes in a genome-wide RNA interference screen and mine the resulting data computationally. Besides confirming existing knowledge, the analysis revealed several regulatory systems, among which were two highly-specific and interconnected feedback circuits, one between the ribosome and the proteasome that controls overall protein homeostasis, and the other between the ribosome and Myc/Max that regulates the protein synthesis capacity of cells. We also identified a set of genes that alter the timing of mitosis without affecting gene expression, indicating that the cyclic transcriptional program that produces the components required for cell division can be partially uncoupled from the cell division process itself. These genes all have a function in a pathway that regulates the phosphorylation state of Cdk1. We provide evidence showing that this pathway is involved in regulation of cell size, indicating that a Cdk1-regulated cell size checkpoint exists in metazoans.
authors: Genome-Scale Biology Research Program, Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
authors: Martin
authors: M
authors: Bonke
authors: Mikko
authors: M
authors: Turunen
authors: Maria
authors: M
authors: Sokolova
authors: Anna
authors: A
authors: Vähärautio
authors: Teemu
authors: T
authors: Kivioja
authors: Minna
authors: M
authors: Taipale
authors: Mikael
authors: M
authors: Björklund
authors: Jussi
authors: J
authors: Taipale
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D048429:Cell Size; D047369:Chromatin Immunoprecipitation; D016000:Cluster Analysis; D004330:Drosophila / Q000235:genetics* / Q000502:physiology; D025461:Feedback, Physiological / Q000502:physiology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000235:genetics*; D046228:Microarray Analysis; D008938:Mitosis / Q000235:genetics; D009841:Oligonucleotides / Q000235:genetics; D010766:Phosphorylation; D034622:RNA Interference; D017423:Sequence Analysis, RNA
chemical_list: D009841:Oligonucleotides; D016203:CDC2 Protein Kinase