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Table 1 Ets1 interacting proteins

From: The Biology of the Ets1 Proto-Oncogene

Proteins that cooperate with Ets1

protein

responsive gene(s)

comments

reference

AML-1

TCRα, TCRβ, osteopontin, GM-CSF

mutual blockage of the negative regulatory domains induces cooperative binding of Ets1 and AML-1

[47–52]

ATF-2

TCRα

binds stronger to Ets1 when it lacks dimerization domain

[48]

AP-1 (c-Jun/c-Fos)

GM-CSF, TIMP-1, polyoma enhancer, MMP-1

 

[53–57]

CBP/p300

MMP-3

 

[42, 58]

ERK1/2

uPA, MMP-3, prolactin

phosphorylates threonine-38

[28, 29, 59, 60]

Ets1

MMP-3

requires presence of a palindromic sequence

[61]

Estrogen receptor

artificial promoter

Ets1 cooperates with unliganded receptor

[62]

GATA3

human interleukin-5

requires presence of PMA and ionomycin

[63]

HIF-2α

VEGFR-2 (Flk-1)

 

[64]

HTLV-I Tax

PTHrP (P3 promoter), interleukin-5

Tax forms ternary complex with Ets1 and Sp1, enhances GATA3/Ets1 cooperation

[63, 65]

LEF-1

TCRα

LEF-1 induces DNA-bending that facilitates Ets1/ATF2 interaction

[48]

c-Myb

α4 integrin, mim-1, lck type I

Ets1/c-Myb synergism blocks repression by ZEB

[66–68]

NFAT

HIV-LTR

 

[69]

NF-κB

GM-CSF, HIV-LTR

 

[56, 69]

Pax5

mb-1

allows Ets1 to bind to unfavorable GGAG, changes contacts of Y395 (H3-helix) with DNA

[70–72]

Pit-1/GHF-1

prolactin

 

[73]

PKCα

PTHrP (P3 promoter)

constitutively active form increases Ets1 activity and induces phosphorylation of exon VII domain

[74]

mutant p53

MDR1

wildtype p53 does not bind to and synergize with Ets1

[75]

wildtype p53

mdm2, bax

requires presence of CBP, and UV-radiation, Ets1 necessary for p53-dependent apoptosis in ES cells

[76]

Ras

uPA, MMP-3, prolactin

induces ERK1/2-dependent phosphorylation of threonine-38

[28, 29]

Smad3/4

PTHrP (P3 promoter)

requires presence of TGFβ

[77]

SPBP

synthetic promoter

SPBP = stromelysin-1 PDGF responsive element binding protein

[78]

Sp1

PTHrP, MRG1, HTLV-I LTR, integrin αIIb, P4 promoter of MVMp, FasL

Ets1/Sp1 bind cooperatively to DNA

[79–83]

Sp100

MMP3, synthetic promoters

does not activate ΔVII-Ets1

[45]

Stat5

GAS/Ets elements

 

[84]

TFE3

immunoglobulin μ heavy-chain gene

basic helix-loop-helix domain of TFE3 sufficient for Ets1 binding, several Ets1 domains involved in binding

[46]

huUBC9

synthetic promoter

 

[85]

USF-1

HIV-LTR

 

[86]

Vitamin D receptor (VDR)

artificial promoter

Ets1 induces conformational change of VDR, in the presence of Ets1 activation by VDR does not require AF2-domain

[62]

Proteins that repress Ets1 activity

protein

responsive gene

comments

reference

CaMKII

GM-CSF

blocks AML-1/Ets1 cooperative effect by phosphorylating exon VII domain

[47]

Daxx/EAPI (Ets1-associated protein)

MMP1 and BCL2

a nuclear protein that cooperates with Ets1 to repress transcription

[87]

EAPII (Ets1-associated protein)

MMP1

a nuclear protein that attenuates Ets1/AP1 cooperative effect, inhibits migration of epithelial cells

[55]

MafB (AP-1 likeprotein)

transferrin receptor, porphobilinogen deaminase

suppresses Ets1-dependent activation of erythoid-specific genes

[88]

ZEB

α4 integrin

repression of Ets1 by ZEB is blocked when Ets1 synergizes with c-Myb

[67]