Figure 3.

Mitogens drive cell cycle progression by induction of cyclinD and inactivation of

the retinoblastoma (Rb) protein. The cell cycle is driven by the co-ordinated activation of the
cyclin-dependent kinases (CDKs). Whereas the CDKs are expressed throughout the cycle, their
activating subunits – the cyclins – oscillate between rapid synthesis and degradation. The
interface between mitogens and the cell cycle is cyclinD (and to a lesser extent cyclinE), whose
expression is induced by mitogens. CyclinD- and cyclinE-dependent kinases phosphorylate (P)
and thereby disable the Rb tumour suppressor protein, which is a principal checkpoint
controlling the progression from G1 to S phase. Inactivation of the Rb protein marks the
restriction point at which cell-cycle progression becomes independent of mitogens. Inactivated
Rb releases E2F transcription factors, which stimulate the expression of downstream cyclins and
other genes that are required for DNA synthesis (fig003wkg).

Gambar 3. Mitogens drive progresi siklus sel oleh induksi cyclinD dan inaktivasi retinoblastoma
tersebut (Rb) protein. Siklus sel ini didorong oleh aktivasi terkoordinasi dari cyclin kinase-
bergantung (CDKs). Sedangkan CDKs disajikan di seluruh siklus, subunit mereka mengaktifkan
- yang siklin - berosilasi antara sintesis cepat dan degradasi. Antarmuka antara mitogens dan
siklus sel cyclinD (dan sampai cyclinE tingkat lebih rendah), yang ekspresinya diinduksi oleh
mitogens. CyclinD-dan cyclinE-tergantung phosphorylate kinase (P) dan dengan demikian
menonaktifkan supresor tumor Rb protein, yang merupakan pos pemeriksaan utama
mengendalikan perkembangan dari G1 ke fase S. Inaktivasi protein Rb menandai titik
pembatasan di mana sel-siklus perkembangan menjadi independen mitogens. Rb dilemahkan rilis
faktor transkripsi E2F, yang merangsang ekspresi gen siklin hilir dan lainnya yang dibutuhkan
untuk sintesis DNA (fig003wkg).