- Mitogenic signaling is required for cells to enter the cell cycle. In the absence of mitogenic signaling, cells stop division and enter a cell cycle stage called quiescence or G0-phase.
- Mitogenic signaling regulates primarily G1 phase progression until the restriction point. Once the cell crosses the restriction point, cell cycle progression becomes independent of mitogenic signaling.
- Mitogenic signaling co-operates with the signaling that emerged from the extracellular matrix to drive cell cycle progression during the G1 phase. In the absence of adhesion (adherent cells in suspension) cells are arrested in the late G1 phase.
- Synthesis of D-type cyclins is the primary purpose of mitogenic signaling. D-type cyclins are the regulatory subunits of CDK4/6. D-type cyclins form complexes with CDK4 (CDK4-cyclin D complex) and CDK6 (CDK6-cyclin D complex). Apparently, mitogenic signaling is also involved in the stability of the cyclin D – CDK4/6 complex. Mitogenic signaling may also help the proper folding of CDK4 and/or CDK6 and their transport to the nucleus.
- D-type cyclins (Cyclin D1 -/-, D2 -/- and D3 -/-) knockout fibroblast still progress in the cell cycle and respond to mitogenic signaling suggesting that there may be a compensatory mechanism for cyclin D regulated by mitogenic signaling.
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