Immune response - ETV3 affect on CSF1-promoted macrophage differentiation

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ETV3 affect on CSF1-promoted macrophage differentiation

CSF1 is involved in proliferation, differentiation and survival of cells of the monocyte/ macrophage lineage.

CSF1 acts via M-CSF receptor and transmits a growth and differentiation signal by activation of RAS signaling pathway [1], [2]. Activated by CSF1 M-CSF receptor binds to GRB2 coupled with SOS1. Activated SOS1 stimulates H-Ras and it leads to ERK1/2 activation through H-Ras/ c-Raf-1/ MEK1(MAP2K1), MEK2(MAP2K2) pathway [3], [4]. Activated ERK1/2 phosphorylates ETS1 and ETS2 [5], [6]. Also, ERK1/2 activation by CSF1 leads to Elk-1 phosphorylation, Elk-1 binds to SRF and stimulates c-Fos transcription [3], [5], [7], [8]. In addition, CSF1 stimulation enhances expression of ETS2 and c-Jun [9], [10]. ETS1, ETS2, c-Jun and c-Fos forms ternary complexes and bind to composite ETS/AP-1 sites in PLAU (UPA) [11], [12] and 08p22/MSR1(CD204) [13], [14] promoters and thus promote macrophage differentiation [10], [15].

Proliferation signaling of CSF1 also involves RAS pathway and leads to ETS2 phosphorylation by ERK1/2. ETS2 binds to monomeric sites in c-Myc, CDK1 (p34) and PRIM2A promoters and thus promoter CSF1 induced proliferation [4], [10].

ETV3 of the ETS-domain family transcription factors that functions as a transcriptional repressor can block mitogenic responses mediated by positively acting Ets factors. ETV3 itself is induced by CSF1, most likely via CSF1 promoted p38 MAPK activation pathway during macrophage differentiation [16]. p38 MAPK stimulates phosphorylation of CREM (activators) and CREB1, probably via MSK1/2 (RPS6KA5/4) [17]. CREM (activators) and CREB1 in turn, activate transcription of ETV3 [18]. Repressor activity of ETV3 is stimulated by binding of DDX20 associated with HDAC2, HDAC5, N-CoR, SMRT and Sin3A [19]. ETV3 can bind only to monomeric ETS sites in PRIM2A, CDK1 (p34) and c-Myc promoters. Thus, it replaces ETS2 and represses promoter activity of proliferative genes. However, it is not able to bind to ETS/AP-1 composite sites, so promoters of differentiation-responsive genes remain unaffected by ETV3 and CSF1-induced cell differentiation goes on and cell proliferation is blocked [10].



Objects list:

08p22/MSR1(CD204) Macrophage scavenger receptor types I and II
CDK1 (p34) Cyclin-dependent kinase 1
CREB1 Cyclic AMP-responsive element-binding protein 1
CREM (activators) cAMP-responsive element modulator
CSF1 Macrophage colony-stimulating factor 1
DDX20 Probable ATP-dependent RNA helicase DDX20
ERK1/2 Erk 1/2 Protein group
ETS1 Protein C-ets-1
ETS2 Protein C-ets-2
ETV3 ETS translocation variant 3
Elk-1 ETS domain-containing protein Elk-1
GRB2 Growth factor receptor-bound protein 2
H-Ras GTPase HRas
HDAC2 Histone deacetylase 2
HDAC5 Histone deacetylase 5
M-CSF receptor Macrophage colony-stimulating factor 1 receptor
MEK1(MAP2K1) Dual specificity mitogen-activated protein kinase kinase 1
MEK2(MAP2K2) Dual specificity mitogen-activated protein kinase kinase 2
MSK1/2 (RPS6KA5/4) MSK1/2(RPS6KA5/4)
N-CoR Nuclear receptor corepressor 1
PLAU (UPA) Urokinase-type plasminogen activator
PRIM2A DNA primase large subunit
SMRT Nuclear receptor corepressor 2
SOS1 Son of sevenless homolog 1
SRF Serum response factor
Sin3A Paired amphipathic helix protein Sin3a
c-Fos Proto-oncogene c-Fos
c-Jun Transcription factor AP-1
c-Myc Myc proto-oncogene protein
c-Raf-1 RAF proto-oncogene serine/threonine-protein kinase
p38 MAPK p38 mitogen-activated protein kinase Protein group

References:

  1. Kharbanda S, Saleem A, Yuan Z, Emoto Y, Prasad KV, Kufe D
    Stimulation of human monocytes with macrophage colony-stimulating factor induces a Grb2-mediated association of the focal adhesion kinase pp125FAK and dynamin. Proceedings of the National Academy of Sciences of the United States of America 1995 Jun 20;92(13):6132-6
  2. Rohrschneider LR, Bourette RP, Lioubin MN, Algate PA, Myles GM, Carlberg K
    Growth and differentiation signals regulated by the M-CSF receptor. Molecular reproduction and development 1997 Jan;46(1):96-103
  3. Hamilton JA
    CSF-1 signal transduction. Journal of leukocyte biology 1997 Aug;62(2):145-55
  4. Cheng M, Wang D, Roussel MF
    Expression of c-Myc in response to colony-stimulating factor-1 requires mitogen-activated protein kinase kinase-1. The Journal of biological chemistry 1999 Mar 5;274(10):6553-8
  5. Yang BS, Hauser CA, Henkel G, Colman MS, Van Beveren C, Stacey KJ, Hume DA, Maki RA, Ostrowski MC
    Ras-mediated phosphorylation of a conserved threonine residue enhances the transactivation activities of c-Ets1 and c-Ets2. Molecular and cellular biology 1996 Feb;16(2):538-47
  6. Chang F, Steelman LS, Lee JT, Shelton JG, Navolanic PM, Blalock WL, Franklin RA, McCubrey JA
    Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 2003 Jul;17(7):1263-93
  7. Hill CS, Treisman R
    Differential activation of c-fos promoter elements by serum, lysophosphatidic acid, G proteins and polypeptide growth factors. The EMBO journal 1995 Oct 16;14(20):5037-47
  8. Yordy JS, Muise-Helmericks RC
    Signal transduction and the Ets family of transcription factors. Oncogene 2000 Dec 18;19(55):6503-13
  9. Langer SJ, Bortner DM, Roussel MF, Sherr CJ, Ostrowski MC
    Mitogenic signaling by colony-stimulating factor 1 and ras is suppressed by the ets-2 DNA-binding domain and restored by myc overexpression. Molecular and cellular biology 1992 Dec;12(12):5355-62
  10. Klappacher GW, Lunyak VV, Sykes DB, Sawka-Verhelle D, Sage J, Brard G, Ngo SD, Gangadharan D, Jacks T, Kamps MP, Rose DW, Rosenfeld MG, Glass CK
    An induced Ets repressor complex regulates growth arrest during terminal macrophage differentiation. Cell 2002 Apr 19;109(2):169-80
  11. Jin DI, Jameson SB, Reddy MA, Schenkman D, Ostrowski MC
    Alterations in differentiation and behavior of monocytic phagocytes in transgenic mice that express dominant suppressors of ras signaling. Molecular and cellular biology 1995 Feb;15(2):693-703
  12. Fowles LF, Martin ML, Nelsen L, Stacey KJ, Redd D, Clark YM, Nagamine Y, McMahon M, Hume DA, Ostrowski MC
    Persistent activation of mitogen-activated protein kinases p42 and p44 and ets-2 phosphorylation in response to colony-stimulating factor 1/c-fms signaling. Molecular and cellular biology 1998 Sep;18(9):5148-56
  13. de Villiers WJ, Fraser IP, Hughes DA, Doyle AG, Gordon S
    Macrophage-colony-stimulating factor selectively enhances macrophage scavenger receptor expression and function. The Journal of experimental medicine 1994 Aug 1;180(2):705-9
  14. Wu H, Moulton K, Horvai A, Parik S, Glass CK
    Combinatorial interactions between AP-1 and ets domain proteins contribute to the developmental regulation of the macrophage scavenger receptor gene. Molecular and cellular biology 1994 Mar;14(3):2129-39
  15. Guidez F, Li AC, Horvai A, Welch JS, Glass CK
    Differential utilization of Ras signaling pathways by macrophage colony-stimulating factor (CSF) and granulocyte-macrophage CSF receptors during macrophage differentiation. Molecular and cellular biology 1998 Jul;18(7):3851-61
  16. Foltz IN, Lee JC, Young PR, Schrader JW
    Hemopoietic growth factors with the exception of interleukin-4 activate the p38 mitogen-activated protein kinase pathway. The Journal of biological chemistry 1997 Feb 7;272(6):3296-301
  17. Deak M, Clifton AD, Lucocq LM, Alessi DR
    Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. The EMBO journal 1998 Aug 3;17(15):4426-41
  18. Sawka-Verhelle D, Escoubet-Lozach L, Fong AL, Hester KD, Herzig S, Lebrun P, Glass CK
    PE-1/METS, an antiproliferative Ets repressor factor, is induced by CREB-1/CREM-1 during macrophage differentiation. The Journal of biological chemistry 2004 Apr 23;279(17):17772-84
  19. Hester KD, Verhelle D, Escoubet-Lozach L, Luna R, Rose DW, Glass CK
    Differential repression of c-myc and cdc2 gene expression by ERF and PE-1/METS. Cell cycle (Georgetown, Tex.) 2007 Jul 1;6(13):1594-604

  1. Kharbanda S, Saleem A, Yuan Z, Emoto Y, Prasad KV, Kufe D
    Stimulation of human monocytes with macrophage colony-stimulating factor induces a Grb2-mediated association of the focal adhesion kinase pp125FAK and dynamin. Proceedings of the National Academy of Sciences of the United States of America 1995 Jun 20;92(13):6132-6
  2. Rohrschneider LR, Bourette RP, Lioubin MN, Algate PA, Myles GM, Carlberg K
    Growth and differentiation signals regulated by the M-CSF receptor. Molecular reproduction and development 1997 Jan;46(1):96-103
  3. Hamilton JA
    CSF-1 signal transduction. Journal of leukocyte biology 1997 Aug;62(2):145-55
  4. Cheng M, Wang D, Roussel MF
    Expression of c-Myc in response to colony-stimulating factor-1 requires mitogen-activated protein kinase kinase-1. The Journal of biological chemistry 1999 Mar 5;274(10):6553-8
  5. Yang BS, Hauser CA, Henkel G, Colman MS, Van Beveren C, Stacey KJ, Hume DA, Maki RA, Ostrowski MC
    Ras-mediated phosphorylation of a conserved threonine residue enhances the transactivation activities of c-Ets1 and c-Ets2. Molecular and cellular biology 1996 Feb;16(2):538-47
  6. Chang F, Steelman LS, Lee JT, Shelton JG, Navolanic PM, Blalock WL, Franklin RA, McCubrey JA
    Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 2003 Jul;17(7):1263-93
  7. Hill CS, Treisman R
    Differential activation of c-fos promoter elements by serum, lysophosphatidic acid, G proteins and polypeptide growth factors. The EMBO journal 1995 Oct 16;14(20):5037-47
  8. Yordy JS, Muise-Helmericks RC
    Signal transduction and the Ets family of transcription factors. Oncogene 2000 Dec 18;19(55):6503-13
  9. Langer SJ, Bortner DM, Roussel MF, Sherr CJ, Ostrowski MC
    Mitogenic signaling by colony-stimulating factor 1 and ras is suppressed by the ets-2 DNA-binding domain and restored by myc overexpression. Molecular and cellular biology 1992 Dec;12(12):5355-62
  10. Klappacher GW, Lunyak VV, Sykes DB, Sawka-Verhelle D, Sage J, Brard G, Ngo SD, Gangadharan D, Jacks T, Kamps MP, Rose DW, Rosenfeld MG, Glass CK
    An induced Ets repressor complex regulates growth arrest during terminal macrophage differentiation. Cell 2002 Apr 19;109(2):169-80
  11. Jin DI, Jameson SB, Reddy MA, Schenkman D, Ostrowski MC
    Alterations in differentiation and behavior of monocytic phagocytes in transgenic mice that express dominant suppressors of ras signaling. Molecular and cellular biology 1995 Feb;15(2):693-703
  12. Fowles LF, Martin ML, Nelsen L, Stacey KJ, Redd D, Clark YM, Nagamine Y, McMahon M, Hume DA, Ostrowski MC
    Persistent activation of mitogen-activated protein kinases p42 and p44 and ets-2 phosphorylation in response to colony-stimulating factor 1/c-fms signaling. Molecular and cellular biology 1998 Sep;18(9):5148-56
  13. de Villiers WJ, Fraser IP, Hughes DA, Doyle AG, Gordon S
    Macrophage-colony-stimulating factor selectively enhances macrophage scavenger receptor expression and function. The Journal of experimental medicine 1994 Aug 1;180(2):705-9
  14. Wu H, Moulton K, Horvai A, Parik S, Glass CK
    Combinatorial interactions between AP-1 and ets domain proteins contribute to the developmental regulation of the macrophage scavenger receptor gene. Molecular and cellular biology 1994 Mar;14(3):2129-39
  15. Guidez F, Li AC, Horvai A, Welch JS, Glass CK
    Differential utilization of Ras signaling pathways by macrophage colony-stimulating factor (CSF) and granulocyte-macrophage CSF receptors during macrophage differentiation. Molecular and cellular biology 1998 Jul;18(7):3851-61
  16. Foltz IN, Lee JC, Young PR, Schrader JW
    Hemopoietic growth factors with the exception of interleukin-4 activate the p38 mitogen-activated protein kinase pathway. The Journal of biological chemistry 1997 Feb 7;272(6):3296-301
  17. Deak M, Clifton AD, Lucocq LM, Alessi DR
    Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. The EMBO journal 1998 Aug 3;17(15):4426-41
  18. Sawka-Verhelle D, Escoubet-Lozach L, Fong AL, Hester KD, Herzig S, Lebrun P, Glass CK
    PE-1/METS, an antiproliferative Ets repressor factor, is induced by CREB-1/CREM-1 during macrophage differentiation. The Journal of biological chemistry 2004 Apr 23;279(17):17772-84
  19. Hester KD, Verhelle D, Escoubet-Lozach L, Luna R, Rose DW, Glass CK
    Differential repression of c-myc and cdc2 gene expression by ERF and PE-1/METS. Cell cycle (Georgetown, Tex.) 2007 Jul 1;6(13):1594-604

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