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biochemistry,
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The retinoblastoma (Rb) gene was the first identified tumor suppressor gene (1). The Rb protein is now recognized to be a central component of a signaling pathway that controls cell proliferation. Specifically the D-type G1 cyclins, together with their associated kinases, Cdk4 and Cdk6, initiate the phosphorylation of Rb and Rb family members, p130 and p107, inactivating their capacity to interact with the E2F transcription factors (Fig. 1). This phosphorylation allows the accumulation of E2F1, E2F2, and E2F3a that activate the transcription of a large number of genes essential for DNA replication as well as further cell cycle progression (2-4). In addition, phosphorylation of Rb and p130 also disrupts complexes with E2F3b, E2F4, and E2F5 found in quiescent cells that function as transcriptional repressors of S phase genes as well as the genes encoding the E2F1, E2F2, and E2F3a proteins (Fig. 1).
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