Phosphoinositide 3-kinase and Forkhead, a switch for cell division.
Cell cycle progression is a tightly controlled process. To initiate cell division, mitogens trigger a number of early signals that promote the G(0)-G(1) transition by inducing cell growth and the activation of G(1) cyclins. Activation of cyclin E/cdk2 (cyclin-dependent kinase 2) at the end of G(1) is then required to trigger DNA synthesis (S phase entry). Among the early signals induced by mitogens, activation of PI3K (phosphoinositide 3-kinase) appears essential to induce cell cycle entry, as it regulates cell growth signalling pathways, which in turn determine the rate of cell cycle progression. Another mechanisms by which PI3K and its downstream effector protein kinase B regulate cell cycle entry is by inactivation of the FOXO (Forkhead Box, subgroup O) transcription factors, which induce expression of quiescence genes such as those encoding p27(kip), p130 and cyclin G2. PI3K/FOXO then work as a complementary switch: when PI3K is active, FOXO transcription factors are inactive. The switch is turned on and off at different phases of the cell cycle, thus regulating cell cycle progression.
Martínez-Gac
L
L
Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Universidad Autónoma de Madrid, Cantoblanco, Madrid E-28049, Spain.
Alvarez
B
B
García
Z
Z
Marqués
M
M
Arrizabalaga
M
M
Carrera
A C
AC
D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002455:Cell Division; D056746:Cyclin G; D056766:Cyclin G1; D056767:Cyclin G2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000378:metabolism; D051858:Forkhead Transcription Factors; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D050717:Retinoblastoma-Like Protein p130; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins
C534702:CCNG1 protein, human; C101593:CCNG2 protein, human; D018797:Cell Cycle Proteins; D056746:Cyclin G; D056766:Cyclin G1; D056767:Cyclin G2; D016213:Cyclins; D051858:Forkhead Transcription Factors; D009687:Nuclear Proteins; D011506:Proteins; D050717:Retinoblastoma-Like Protein p130; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D019869:Phosphatidylinositol 3-Kinases