Cell-intrinsic timer

Durand B, Gao FB, Raff M 1997 Accumulation of the cyclin-dependent kinase inhibitor p27/ Kipl and the timing of oligodendrocyte differentiation. EMBO J 16 306-317 Durand B, Fero ML, Roberts JM, Raff MC 1998 p27Kipl alters the response of cells to mitogen and is part of a cell-intrinsic timer that arrests the cell cycle and initiates differentiation. Curr Biol 8 431-440... 

Raff Yes, it is very unlikely that it is counting divisions. I don t think that cell-intrinsic timers are responsible for all of timing in development. It is quite clear that they are not. But cells do change as they develop, and some of the changes seem to reflect intrinsic programmes operating within the cells. 

Durand B, Raff M (2000) A cell-intrinsic timer that operates during oligodendrocyte development. 

Burton PBJ, Raff MC, Kerr P, Yacoub MH, Barton PJR 1999 An intrinsic timer that controls cell-cycle withdrawal in cultured cardiac myocytes. Dev Biol 216 659—670 Chen X, Ko LJ, Jayaraman L, Prives C 1996 p53 levels, functional domains, and DNA damage determine the extent of the apoptotic response of tumor cells. Genes Dev 10 2438—2451 Duesbery NS, Choi T, Brown KD et al 1997 CENP-E is an essential kinetochore motor in maturing oocytes and is masked during mos-dependent cell cycle arrest at metaphase II. Proc Natl Acad Sci USA 94 9165-9170... 

Although the timer is cell-intrinsic, it requires signals from other cells to operate normally. It depends on PDGF, for example, the main mitogen for OPCs. The... 

It is uncertain whether the intrinsic timer in OPCs primarily controls the onset of differentiation, the cessation of proliferation, or both. It seems likely, however, that the timer at some point interacts with the cell-cycle control system that regulates progress through the cell cycle. As the cells stop dividing and differentiate in Gl, it is the part of the control system that operates in G1 that is most likely to be relevant. In principle, the components of the cell-cycle control system could be components of the timer. The timer, for example, could depend on a decrease in one or more positive intracellular regulators, such as a cyclin or a Cdk... 

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