Identification of cyclin A2 as the downstream effector of the nuclear phosphatidylinositol 4,5-bisphosphate signaling network.
In addition to the well characterized phosphoinositide second messengers derived from the plasma membrane, increasing evidence supports the existence of a nuclear phosphoinositide signaling network. The aim of this investigation was to dissect the role played by nuclear phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) in cell cycle progression and to determine the cell cycle regulatory component(s) that are involved. A number of cytosolic/nuclear PtdIns(4,5)P2-deficient Swiss 3T3 cell lines were established, and their G 0/G 1/S cell cycle phase transitions induced by defined mitogens were examined. Our results demonstrate that nuclear PtdIns(4,5)P2 down-regulation caused a delay in phorbol ester-induced S phase entry and that this was at least in part channeled through cyclin A2 at the transcriptional level. In summary, these data identify cyclin A2 as a downstream effector of the nuclear PtdIns(4,5)P2 signaling network and highlight the importance of nuclear PtdIns(4,5)P2 in the regulation of mammalian mitogenesis.
Ho
Ka-Kei
KK
Division of Cell and Molecular Biology, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom.
Anderson
Alexandra A
AA
Rosivatz
Erika
E
Lam
Eric W-F
EW
Woscholski
Rüdiger
R
Mann
David J
DJ
D016475:3T3 Cells; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D019925:Cyclin A / Q000096:biosynthesis* / Q000378:metabolism; D056751:Cyclin A2; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D016196:S Phase / Q000187:drug effects / Q000502:physiology*; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*
C508184:CCNA2 protein, mouse; D019925:Cyclin A; D056751:Cyclin A2; D019269:Phosphatidylinositol 4,5-Diphosphate