Table 11-1
CDKs, Activating Cyclins, and Select Substrates
CDK | Cyclin Partner | Substrate |
CDKi (CDC2) | A and B | Lamins, histone Hi |
CDK2 | E and A | Rb, P107, P130, Cdt1, CP110 |
CDK3 | C | Rb |
CDK4 | D | Rb, P107, P130, SMAD2, and SMAD3 |
CDK6 | D | Rb, P107, P130, SMAD2, and SMAD3 |
CDK7 (CAK) | H | CDK1-CDK6, RNA pol 11 |
CDK, Cyclin-dependent kinase.


CDK Regulation by Small-Polypeptide Inhibitors
Ink4 Family

Cip/Kip Family

Transcriptional Regulation by the E2F Transcription Factors

G1 Regulation/Restriction Point Control

Regulation of DNA Replication (S Phase)

G2/M Transition Regulation
The Kinases of Mitosis
Table 11-2
Regulators of DNA Replication and Function
Cdt1 | Associates with MCM2-MCM7 and, in concert with Cdc6, facilitates MCM loading on origins. |
Cdc6 | Functions to recruit and load the MCM complex in an ATPase-dependent manner. |
CdC45 | Associates with the MCM and is responsible for recruitment of DNA polymerase α, primase, and replication protein A. |
MCM2-7 | Minichromosome maintenance proteins. Hetero-hexameric complex composed of six distinct but related proteins (MCM2-MCM7). The MCM complex functions as the putative replicative helicase. |
MCM10 | Structurally distinct from MCM2-MCM7; functions to recruit CDC45. |
Orc | Origin recognition complex. Hetero-hexameric complex that binds directly to DNA and functions as a protein landing pad on which the replication complexes form. |
Origin | Functionally defined in mammalian cells as regions of chromatin where DNA replication initiates. |
Cdc7/Dbf4 | The Cdc7 protein kinase, like cyclin-dependent kinases (CDKs), requires an allosteric activator, Dbf4. The Cdc7/Dbf4 kinase phosphorylates components of the replication complexes to initiate DNA replication. |
Pre-RC | The prereplication forms during G1 and contains ORC1-ORC6, Cdc6, MCM2-7. Replication ensues at S phase on recruitment of DNA polymerase and phosphorylation by both the Cdc7/Dbf4 and CDK2-cyclin A protein kinases. |
MCM, Minichromosome maintenance; ORC, origin of replication complex.
Entry into Mitosis
Chromosome Cohesion
Exit from Mitosis

Mitotic Checkpoint
Regulated Proteolysis in Cell Cycle Control

SCF Ligases
APC/C Ligase

Sumoylation
Integration of Growth Factor Signals During G1 Phase by the Ras Small GTP-Binding Protein
Deregulation of G1 Restriction Point Control in Cancer
Targeting the Cell Cycle as a Therapeutic Modality
Targeting CDKs
Targeting Cell Cycle Checkpoints
Targeting Regulators of Mitosis
Conclusions
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