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Table 1 Proteins modeled in the cell-cycle model.

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

  

inhibits cyclins--prevent S

2

Rb

N

high

 

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

 

activates Cdk4or6 kinase; inactivates APC(Cdh1)

4

Cdk2

N

high

 

constitutive, E2F

cycE, cycA, Cdc25A

 

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*

 

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**

 

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

 

ubiquitinase (requires subunit)

11

Skp2

N

0

auto (when no Emi1 or Wee1), APC(Cdh1)

constitutive

SCF

 

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

 

ubiquitinase subunit for Emi1, Cdc25A (sometimes), Wee1, others

13

Fbw7

N

0

auto (when no cycE, TF-grow**, or RC**)

E2F

SCF

 

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

  

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

 

E2F, B-Myb, NF-Y*, inhibits itself*

RC

 

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

 

activate Cdk1 kinase

19

Cdk1

CN

high*

 

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

 

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*

 

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

 

cycB/Cdk1, cycA/Cdk1*

inhibits Cdh1, Cdc20

23

APC

N

high

 

constitutive

Cdh1, Cdc20

 

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

 

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

  

keeps separase from destroying chromotin cohesion proteins

30

cycC

N

high

 

constitutive

Cdk8, Cdc14*

mitogen*

inhibits RNA pol

31

KPC

N

  

constitutive

mitogen

 

ubiquitinase for p27

32

RNA poly

N

high

 

constitutive, TF_grow*

mitogen*

cycC/Cdk8, APC(Cdc20)*

txs

33

eIF-4

C

high

 

constitutive

mRNA

 

initiates txl

  1. The proteins represent different layers of abstraction (see Additional file 1). LOC = location, N = nucleus, C = cytoplasm, G0 = steady-state concentration, UBIQ = ubiquitinating molecules, auto = autoubiquitination, INDUCER = molecule effecting transcription, ACTIVATOR = molecule promoting activity, TF = transcription factor, txs = transcription, txl = translation, ? = unknown, * = assumed, ** = ignored.