The intraflagellar transport component IFT88/polaris is a centrosomal protein regulating G1-S transition in non-ciliated cells.
Loss of normal primary cilia function in mammals is linked to proliferative diseases, such as polycystic kidney disease, suggesting a regulatory relationship between cilia and cell cycle. The primary cilium expressed by most mammalian cells is nucleated from the elder centriole of the centrosome. The relationship between centrosome and cilia suggests that these structures share functions and components. We now show that IFT88/polaris, a component of the intraflagellar transport, remains associated to the centrosome in a proliferative state. IFT88/polaris is tightly associated with the centrosome throughout the cell cycle in a microtubule- and dynein-independent manner. IFT88/polaris tetratricopeptide repeat motifs are essential for this localization. Overexpression of IFT88/polaris prevents G1-S transition and induces apoptotic cell death. By contrast, IFT88/polaris depletion induced by RNA interference promotes cell-cycle progression to S, G2, and M phases. Finally, we demonstrate that IFT88/polaris interacts with Che-1, an Rb-binding protein that inhibits the Rb growth suppressing function. We propose that IFT88/polaris, a protein essential for ciliogenesis, is also crucial for G1-S transition in non-ciliated cells.
Robert
Aude
A
Institut Cochin, Département Génétique et Développement, Faculté de médecine R. Descartes, UM 3, Paris, F-75014 France.
Margall-Ducos
Germain
G
Guidotti
Jacques-Emmanuel
JE
Brégerie
Olivier
O
Celati
Claude
C
Bréchot
Christian
C
Desdouets
Chantal
C
D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D018385:Centrosome / Q000378:metabolism*; D005407:Flagella / Q000378:metabolism*; D016193:G1 Phase / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D010940:Plant Proteins; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016196:S Phase / Q000502:physiology*
C416363:IFT88 protein, Chlamydomonas; D010940:Plant Proteins; D015800:Protozoan Proteins; D049452:Green Fluorescent Proteins