Proliferation, but not growth, blocked by conditional deletion of 40S ribosomal protein S6.
Because ribosome biogenesis plays an essential role in cell proliferation, control mechanisms may have evolved to recognize lesions in this critical anabolic process. To test this possibility, we conditionally deleted the gene encoding 40S ribosomal protein S6 in the liver of adult mice. Unexpectedly, livers from fasted animals deficient in S6 grew in response to nutrients even though biogenesis of 40S ribosomes was abolished. However, liver cells failed to proliferate or induce cyclin E expression after partial hepatectomy, despite formation of active cyclin D-CDK4 complexes. These results imply that abrogation of 40S ribosome biogenesis may induce a checkpoint control that prevents cell cycle progression.
Volarevic
S
S
Friedrich Miescher Institute, Maulbeerstrasse 66, CH-4058, Basel, Switzerland.
Stewart
M J
MJ
Ledermann
B
B
Zilberman
F
F
Terracciano
L
L
Montini
E
E
Grompe
M
M
Kozma
S C
SC
Thomas
G
G
D000818:Animals; D002455:Cell Division; D019938:Cyclin D1 / Q000096:biosynthesis / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D005508:Food Deprivation; D016193:G1 Phase; D017353:Gene Deletion; D018390:Gene Targeting; D006498:Hepatectomy; D016898:Interferon-alpha / Q000494:pharmacology; D008099:Liver / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D008115:Liver Regeneration; D051379:Mice; D008815:Mice, Inbred Strains; D010766:Phosphorylation; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012335:RNA, Ribosomal / Q000378:metabolism; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins / Q000235:genetics / Q000502:physiology*; D012270:Ribosomes / Q000378:metabolism; D016196:S Phase
D019927:Cyclin E; D016898:Interferon-alpha; D011518:Proto-Oncogene Proteins; D012335:RNA, Ribosomal; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins; D019938:Cyclin D1; D004247:DNA; D017346:Protein Serine-Threonine Kinases; C495902:Cdk4 protein, mouse; C495912:Cdk6 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases