1. XXXX Mitogenic signals  Ras myc Cyclin DCDK4/6 Rb E2F myc p16 INK4 p14 ARF p53 p21 p27Cyclin ECDK2 Cyclin ACDK2 DNA Replication ATMmdm2 PKB Master Switch E2F DNA Replication Factors Senescence / Apoptosis DNA Repair TGF-β TGF-β Early-Mid G 1 Restriction Pt. Late G 1 S S BRCA2 BCL-2 Bax All pathways DNA Damage Click on any yellow box Go to next pathway Previous pathway Return to main page Red = inhibits cell growth Green = increases cell growth Line = inhibits next step Arrow = leads to next step End show Click to continue

2. XXXX Mitogenic signals  Ras Mitogenic signals  Ras myc Cyclin D CDK4/6 Rb E2F myc p16 INK4 p14 ARF p53 p21 p27 Cyclin E CDK2 Cyclin A CDK2 DNA Replication ATM mdm2 PKB Master Switch Master Switch E2F DNA Replication Factors Senescence / Apoptosis DNA Repair TGF-β TGF-β TGF-β TGF-β Early-Mid G 1 Restriction Pt. Late G 1 S S BRCA2 BCL-2 Bax All pathways DNA Damage DNA Damage

3. XXXX Mitogenic signals  Ras myc Cyclin D CDK4/6 Rb E2F Cyclin E CDK2 Cyclin A CDK2 DNA Replication Master Switch E2F DNA Replication Factors Early-Mid G 1 Restriction Pt. Late G 1 S S Mitogen

4. XXXX myc Cyclin D CDK4/6 Rb E2F myc p16 INK4 p14 ARF p53 p21 Cyclin E CDK2 Cyclin A CDK2 DNA Replication Master Switch E2F DNA Replication Factors Senescence / Apoptosis DNA Repair Early-Mid G 1 Restriction Pt. Late G 1 S S BCL-2 Bax myc

5. XXXX Rb E2F Cyclin E CDK2 Cyclin A CDK2 DNA Replication Master Switch E2F DNA Replication Factors Early-Mid G 1 Restriction Pt. Late G 1 S S Master Switch

6. XXXX p53 p21 Cyclin E CDK2 ATM mdm2 Senescence / Apoptosis DNA Repair Early-Mid G 1 Restriction Pt. Late G 1 S S BRCA2 BCL-2 Bax DNA damage DNA Damage

7. XXXX p53 p21 p27 Cyclin E CDK2 PKB Senescence / Apoptosis DNA Repair Early-Mid G 1 Restriction Pt. Late G 1 S S BCL-2 Bax PKB

8. XXXX p16 INK4 p27 Cyclin E CDK2 Senescence / Apoptosis TGF-β Early-Mid G 1 Restriction Pt. Late G 1 S S TGF-β