From: A general framework for modeling growth and division of mammalian cells
 | PROTEIN | LOC | G0 | UBIQ | INDUCER | ACTIVATOR | INACTIVATOR | FUNCTION |
---|---|---|---|---|---|---|---|---|
1 | p27 | N | high | KPC, SCF(Skp2), APC(Cdc20) | constitutive | Â | Â | inhibits cyclins--prevent S |
2 | Rb | N | high | Â | constitutive, E2F inhibits | Cdc14* | cycD/Cdk4or6, cycE/Cdk2, cycA/Cdk2, cycA/Cdk1, cycB/Cdk1 | inhibits E2F |
3 | cycD | N | 0 | SCF(Skp2), APC(Cdc20)* | mitogen, B-Myb* | Cdk4or6 | Â | activates Cdk4or6 kinase; inactivates APC(Cdh1) |
4 | Cdk2 | N | high | Â | constitutive, E2F | cycE, cycA, Cdc25A | Â | kinase--phosphorylates RC--allows DNA replication |
5 | cycE | N | 0 | SCF(Fbw7)--on Cdk2, SCF(Skp2)--free | E2F | Cdk2 | p27 | activates Cdk2 kinase |
6 | B-Myb | N | 0 | SCF(Skp2)--free | E2F, B-Myb | cycA/Cdk2, cycE/Cdk2* | Â | TF for cycD, Cdk1, Plk1, DNA pol, B-Myb, TF-grow, others |
7 | NF-Y | N | 0 | ? | constitutive, E2F | cycA/Cdk2, cycE/Cdk2* | Cdc14* | TF for cycA, cycB, Cdk1, Cdc25C, TF-grow |
8 | E2F | N | 0 | SCF(Skp2), APC(Cdc20)* | constitutive, E2F, B-Myb inhibits** | Â | Rb, cycB/Cdk1, cycA/Cdk2**, cycA/Cdk1**, cycD/Cdk4or6** | TF for cycE, cycA, Rb, Cdk1, Cdk2, E2F, Cdk25A, DNA pol, others |
9 | cycA | N | 0 | APC(Cdh1), SCF(Skp2)**, APC(Cdc20)** | E2F, NF-Y, mitogen, adhesion** | Cdk2, Cdc25A, Cdk1, Cdc25A, Cdc25B, Cdc25C | p27 (for cycA/Cdk2), Wee1 (for cycA/Cdk1) | activates Cdk2 and Cdk1 kinases |
10 | SCF | CN | 0 | APC(Cdh1) | constitutive | Skp2, Btrc, Fbw7 | Â | ubiquitinase (requires subunit) |
11 | Skp2 | N | 0 | auto (when no Emi1 or Wee1), APC(Cdh1) | constitutive | SCF | Â | ubiquitinase subunit for p27, E2F, RC, TF-grow, B-Myb, free cycE, cycA, cycD, others |
12 | Btrc | C | 0 | auto (when no p27, cycE, E2F, or RC), APC(Cdh1), APC(Cdc20) | E2F | SCF | Â | ubiquitinase subunit for Emi1, Cdc25A (sometimes), Wee1, others |
13 | Fbw7 | N | 0 | auto (when no cycE, TF-grow**, or RC**) | E2F | SCF | Â | ubiquitinase subunit for cycE, TF-grow, RC** |
14 | TF-grow (e.g., c-myc, c-Jun, Notch) | N | 0 | SCF(Skp2), SCF(Fbw7) (not ubiquitinated while TF-grow is on DNA)* | mitogen, Skp2, B-Myb | Â | Â | TF for cell growth |
15 | RC (e.g., hORC1, hCdc6) | N | 0 | SCF(Fbw7)**, SCF(Skp2), APC(Cdh1) | E2F | cycE/Cdk2, cycA/Cdk2, cycD/Cdk4or6 | cycA/Cdk1, p27 | DNA replication complex |
16 | DNA poly | N | 0 | Â | E2F, B-Myb, NF-Y*, inhibits itself* | RC | Â | DNA polymerase |
17 | Wee1 | C | high | SCF(Btrc) | constituitive | Cdc14 | cycA/Cdk2**, cycA/Cdk1**, cycB/Cdk1**, Plk1 | kinase--prevents Cdk1 activation |
18 | cycB | CN | 0 | APC(Cdc20), APC(Cdh1) | E2F, B-Myb, NF-Y | Cdk1 | Â | activate Cdk1 kinase |
19 | Cdk1 | CN | high* | Â | E2F, B-Myb, NF-Y, constitutive | cycA, cycB, B-Myb, NF-Y, Plk1, Cdc25A, Cdc25B, Cdc25C | Wee1, Cdc14 | kinase--activates APC(Cdc20) |
20 | Cdc25C | CN | high | Â | constitutive, NF-Y** | cycB/Cdk1, Plk1, cycA/Cdk1* | Cdc14 | phosphatase--activates cycB/Cdk1 |
21 | Plk1 | C | 0 | APC(Cdh1) | E2F, TF-grow | cycB/Cdk1, cycA/Cdk1* | Â | kinase--activates Cdc25C; deactivates Emi1, Wee1; translocates cycA/Cdk1, cycB/Cdk1, Cdc25C, and Plk1 to nucleus |
22 | Emi1 | CN | 0 | SCF(Btrc), SCF(Skp2)* | E2F | Â | cycB/Cdk1, cycA/Cdk1* | inhibits Cdh1, Cdc20 |
23 | APC | N | high | Â | constitutive | Cdh1, Cdc20 | Â | ubiquitinase (requires subunit) |
24 | Cdh1 | N | high | auto (when no Skp2, cycA, cycB, Cdc25A, Plk1, RC, Cdc20, SCF*, p27**) | constitutive | APC, Cdc14 | Emi1, cycA/Cdk2, cycB/Cdk1, cycD/Cdk4or6, cycE/Cdk2 | ubiquitinase subunit--maintains G0, G1--ubiq Cdc20, cycA (free), cycB (free), Cdc25A, RC, Plk1, Skp2, others |
25 | Cdc20 | N | 0 | APC(Cdh1) | constitutive | APC, cycB/Cdk1, cycA/Cdk1* | Emi1, Cdc14 | ubiquitinase subunit for Securin, cycB, cycA |
26 | Cdc14 (represents MEN pathway) | N | high | Â | constitutive | Plk1* | Securin | phosphatase--ends M--activates p27, Wee1, Cdh1; deactivates Cdc25A, Cdc25B, Cdc25C |
27 | Cdc25A | N | 0 | APC(Cdh1), SCF(Btrc)* | constitutive, E2F, TF-grow | cycE/Cdk2, cycA/Cdk2, cycA/Cdk1*, cycB/Cdk1* | Cdc14 | phosphatase--activates cycE/Cdk2, cycA/Cdk2, cycA/Cdk1*, cycB/Cdk1* |
28 | Cdc25B | C | 0 | APC(Cdh1)*, SCF(Btrc)* | E2F*, TF-grow*, | TF-grow**, cycA/Cdk1*, cycB/Cdk1* | Cdc14 | phosphatase--activates cycA/Cdk1, cycB/Cdk1* |
39 | Securin | N | 0 | APC(Cdc20) | E2F | Â | Â | keeps separase from destroying chromotin cohesion proteins |
30 | cycC | N | high | Â | constitutive | Cdk8, Cdc14* | mitogen* | inhibits RNA pol |
31 | KPC | N | Â | Â | constitutive | mitogen | Â | ubiquitinase for p27 |
32 | RNA poly | N | high | Â | constitutive, TF_grow* | mitogen* | cycC/Cdk8, APC(Cdc20)* | txs |
33 | eIF-4 | C | high | Â | constitutive | mRNA | Â | initiates txl |