Mapk

Y cascade i

Phosphorylation of Jun and Fos in nucleus

Phosphorylation of Jun and Fos in nucleus

CDKs factor E2F

G1 to S phase

FIGURE 12-45 Regulation of cell division by growth factors. The path from growth factors to cell division leads through the enzyme cascade that activates MAPK; phosphorylation of the nuclear transcription factors Jun and Fos; and the activity of the transcription factor E2F, which promotes synthesis of several enzymes essential for DNA synthesis.

G1 to S phase

FIGURE 12-45 Regulation of cell division by growth factors. The path from growth factors to cell division leads through the enzyme cascade that activates MAPK; phosphorylation of the nuclear transcription factors Jun and Fos; and the activity of the transcription factor E2F, which promotes synthesis of several enzymes essential for DNA synthesis.

the nucleus to activate transcription of their genes. Synthesis of E2F is in turn regulated by extracellular signals such as growth factors and cytokines (inducers of cell division), compounds found to be essential for the division of mammalian cells in culture. These growth factors induce the synthesis of specific nuclear transcription factors essential to the production of the enzymes of DNA synthesis. Growth factors trigger phosphorylation of the nuclear proteins Jun and Fos, transcription factors that promote the synthesis of a variety of gene products, including cyclins, CDKs, and E2F. In turn, E2F controls production of several enzymes essential for the synthesis of deoxynucleotides and DNA, enabling cells to enter the S phase (Fig. 12-45).

Inhibition of CDKs Finally, specific protein inhibitors bind to and inactivate specific CDKs. One such protein is p21, which we discuss below.

These four control mechanisms modulate the activity of specific CDKs that, in turn, control whether a cell will divide, differentiate, become permanently quiescent, or begin a new cycle of division after a period of quiescence. The details of cell cycle regulation, such as the number of different cyclins and kinases and the combinations in which they act, differ from species to species, but the basic mechanism has been conserved in the evolution of all eukaryotic cells.

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