Regulation of IL6 transcription

Stable Identifier
R-HSA-3790130
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
extracellular region, nucleoplasm
ReviewStatus
5/5
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Regulation of IL6 transcription
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Methylation of the IL6 promoter by EHMT1:EHMT2 (GLP:G9a) histone methyltransferases inhibits IL6 transcription, while Cdh1:APC/C-mediated degradation of EHTM1:EHTM2 downstream of the ATM-TP53-CDKN1A axis stimulates IL6 transcription (Takahashi et al. 2012). Oncogenic RAS signaling stimulates activation of the CEBPB transcription factor (C/EBP-beta) which binds IL6 promoter and stimulates IL6 transcription (Kuilman et al. 2008, Lee et al. 2010). NF kappa B transcription factor is also activated in senescent cells (Chien et al. 2011) through interleukin-1-alpha (IL1A) signaling (Jimi et al. 1996, Hartupee et al. 2008, Orjalo et al. 2009), and it cooperates with CEBPB in the activation of IL6 transcription (Shimizu et al. 1990, Libermann and Baltimore 1990, Matsusaka et al. 1993, Acosta et al. 2008). Autocrine IL6 signaling stimulates CEBPB expression (Kuilman et al. 2008), creating a positive feedback loop. STAT3, activated by IL6 signaling cascade is necessary for CEBPB transcription, but the direct binding of STAT3 to the CEBPB promoter has not been demonstrated (Niehof et al. 2001).
VENTX inhibits transcription of the Interleukin-6 (IL6) gene, thus promoting differentiation of primary monocytes into dendritic cells (Wu et al. 2014). The NFKB complex which competes with VENTX for binding to the IL6 gene promoter (Wu et al. 2014). It is not known whether histone H3K9 dimethylation at the VENTX promoter (Takahashi et al. 2012) is involved in VENTX-mediated transcriptional repression of IL6.
Literature References
PubMed ID Title Journal Year
20351173 RSK-mediated phosphorylation in the C/EBP{beta} leucine zipper regulates DNA binding, dimerization, and growth arrest activity

Lee, S, Shuman, JD, Guszczynski, T, Sakchaisri, K, Sebastian, T, Copeland, TD, Miller, M, Cohen, MS, Taunton, J, Smart, RC, Xiao, Z, Yu, LR, Veenstra, TD, Johnson, PF

Mol. Cell. Biol. 2010
8617720 Interleukin-1 alpha activates an NF-kappaB-like factor in osteoclast-like cells

Jimi, E, Ikebe, T, Takahashi, N, Hirata, M, Suda, T, Koga, T

J. Biol. Chem. 1996
18555777 Chemokine signaling via the CXCR2 receptor reinforces senescence

Acosta, JC, O'Loghlen, A, Banito, A, Guijarro, MV, Augert, A, Raguz, S, Fumagalli, M, Da Costa, M, Brown, C, Popov, N, Takatsu, Y, Melamed, J, d'Adda di Fagagna, F, Bernard, D, Hernando, E, Gil, J

Cell 2008
2183031 Activation of interleukin-6 gene expression through the NF-kappa B transcription factor

Libermann, TA, Baltimore, D

Mol. Cell. Biol. 1990
22178396 DNA damage signaling triggers degradation of histone methyltransferases through APC/C(Cdh1) in senescent cells

Takahashi, A, Imai, Y, Yamakoshi, K, Kuninaka, S, Ohtani, N, Yoshimoto, S, Hori, S, Tachibana, M, Anderton, E, Takeuchi, T, Shinkai, Y, Peters, G, Saya, H, Hara, E

Mol. Cell 2012
11114305 Interleukin-6-induced tethering of STAT3 to the LAP/C/EBPbeta promoter suggests a new mechanism of transcriptional regulation by STAT3

Niehof, M, Streetz, K, Rakemann, T, Bischoff, SC, Manns, MP, Horn, F, Trautwein, C

J. Biol. Chem. 2001
20452968 CCAAT/Enhancer-binding protein beta DNA binding is auto-inhibited by multiple elements that also mediate association with p300/CREB-binding protein (CBP)

Lee, S, Miller, M, Shuman, JD, Johnson, PF

J. Biol. Chem. 2010
18411265 Interleukin 1alpha-induced NFkappaB activation and chemokine mRNA stabilization diverge at IRAK1

Hartupee, J, Li, X, Hamilton, T

J. Biol. Chem. 2008
2405250 Involvement of a NF-kappa B-like transcription factor in the activation of the interleukin-6 gene by inflammatory lymphokines

Shimizu, H, Mitomo, K, Watanabe, T, Okamoto, S, Yamamoto, K

Mol. Cell. Biol. 1990
19805069 Cell surface-bound IL-1alpha is an upstream regulator of the senescence-associated IL-6/IL-8 cytokine network

Orjalo, AV, Bhaumik, D, Gengler, BK, Scott, GK, Campisi, J

Proc. Natl. Acad. Sci. U.S.A. 2009
8234276 Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8

Matsusaka, T, Fujikawa, K, Nishio, Y, Mukaida, N, Matsushima, K, Kishimoto, T, Akira, S

Proc. Natl. Acad. Sci. U.S.A. 1993
21979375 Control of the senescence-associated secretory phenotype by NF-?B promotes senescence and enhances chemosensitivity

Chien, Y, Scuoppo, C, Wang, X, Fang, X, Balgley, B, Bolden, JE, Premsrirut, P, Luo, W, Chicas, A, Lee, CS, Kogan, SC, Lowe, SW

Genes Dev. 2011
18555778 Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network

Kuilman, T, Michaloglou, C, Vredeveld, LC, Douma, S, van Doorn, R, Desmet, CJ, Aarden, LA, Mooi, WJ, Peeper, DS

Cell 2008
24706756 Homeobox transcription factor VentX regulates differentiation and maturation of human dendritic cells

Wu, X, Gao, H, Bleday, R, Zhu, Z

J. Biol. Chem. 2014
Participants
Input
Output
Participates
as an event of
This event is regulated
Negatively by
Regulator
VENTX:IL6 Gene [nucleoplasm] (Homo sapiens)
Active Unit
VENTX [nucleoplasm]
Regulator
EHMT1:EHMT2 [nucleoplasm] (Homo sapiens)
Positively by
Regulator
Cdh1:phospho-APC/C complex [nucleoplasm] (Homo sapiens)
Regulator
p-T235,S321-CEBPB:NF-kB:IL6 gene [nucleoplasm] (Homo sapiens)
Active Unit
NFKB1(1-433):RELA [nucleoplasm]
p-T235,S321-CEBPB homodimer [nucleoplasm]
Authored
Orlic-Milacic, M  (2013-07-15)
Reviewed
Samarajiwa, S  (2013-09-03)
Vegi, NM  (2019-10-18)
Created
Orlic-Milacic, M  (2013-07-05)
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