Mdm4

Mdm2

HAUSP

1:

BT2

0

2:

BT4

74

4:

BT5

49

5:

CA

MA

-1

6:

DU

44

75

7:

EV

SA

-T

8:

HC

C1

937

9:

Hs5

78

T

p53

p300

pRB

ATM

CBP

p16

p21

p14ARF

Tropomysosin

Tubulin

PUMA

CDK4

Cyclin D1

10:

MC

F-7

12:

MD

A-M

B-1

57

11:

MD

A-M

B-1

34V

I

13:

MD

A-M

B-1

75V

II

14:

MD

A-M

B-2

31

15:

MD

A-M

B-3

30

16:

MD

A-M

B-3

61

17:

MD

A-M

B-4

15

18:

MD

A-M

B-4

35S

19:

MD

A-M

B-4

36

20:

MD

A-M

B-4

53

21:

MD

A-M

B-4

68

23B

: O

CU

B-M

22:

MPE

60

0

24:

SK

-BR

-3

25:

SK

-BR

-5

26:

SK

-BR

-7

27:

SU

M4

4PE

28:

SU

M5

2PE

30:

SU

M1

49PT

31:

SU

M1

59PT

32:

SU

M1

85PE

33:

SU

M1

90PT

34:

SU

M2

25C

WN

35:

SU

M2

29PE

36:

SU

M1

315

M0

2

37:

T4

7D

38:

UA

CC

-81

2

39:

UA

CC

-89

3

40:

ZR

75

-1

41:

ZR

75

-30

Supplementary Figure 1

MPE600

0 24 48 720.0

0.5

1.0

1.5

2.0

2.5

Time (hours)

Rela

tive g

row

th

MCF-7

0 24 48 720

1

2

3

4

Time (hours)

Rela

tive g

row

th

ZR75-1

0 24 48 720

1

2

3

Time (hours)

Rela

tive g

row

th

ZR75-30

0 24 48 720.0

0.5

1.0

1.5

2.0

Time (hours)

Rela

tive g

row

th

C D

A B

Supplementary Figure 2

***

**

*

******

***

*****

***

***

***

*** ***

* **

******

*********

*

**

***

***

***

MCF-7

0 24 48 720

1

2

3

4

5

Time (hours)

Rela

tive g

row

th

MPE600

0 24 48 720

1

2

Time (hours)

Rela

tive g

row

th

ZR75-1

0 24 48 720

1

2

3

Time (hours)

Rela

tive g

row

th

ZR75-30

0 24 48 720

1

2

Time (hours)

Rela

tive g

row

th

Supplementary Figure 3

A

DC

B

Mdm2

Mdm4

pSer15-p53

pSer46-p53

p53

PUMA

p21

HAUSP

Doxorubicin

+ 10 µM Nutlin-3

0 0.05 0.1 0.2 0.3 0.4 0.50.0

0.2

0.4

0.6

0.8

1.0

1.2

-

+ Nutlin-3

Doxorubicin (M)

Rela

tive c

ell

nu

mber

Supplementary Figure 4