Stimulation of IL8 transcription in senescent cells

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R-HSA-3790137
Type
Reaction [omitted]
Species
Homo sapiens
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Methylation of the IL8 promoter by EHMT1:EHMT2 (GLP:G9a) histone methyltransferases inhibits IL8 transcription, while Cdh1:APC/C-mediated degradation of EHTM1:EHTM2 downstream of the ATM-TP53-CDKN1A axis stimulates IL8 transcription (Takahashi et al. 2012). CEBPB transcription factor, activated by oncogenic RAS signaling, binds IL8 promoter and stimulates IL8 transcription (Kuilman et al. 2008). The 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 IL8 transcription (Kunsch and Rosen 1993, Stein and Baldwin 1993, Matsusaka et al. 1993, Acosta et al. 2008).

Literature References
PubMed ID Title Journal Year
8413306 Distinct mechanisms for regulation of the interleukin-8 gene involve synergism and cooperativity between C/EBP and NF-kappa B

Stein, B, Baldwin, AS

Mol. Cell. Biol. 1993
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
18411265 Interleukin 1alpha-induced NFkappaB activation and chemokine mRNA stabilization diverge at IRAK1

Hartupee, J, Li, X, Hamilton, T

J. Biol. Chem. 2008
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
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
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
8413215 NF-kappa B subunit-specific regulation of the interleukin-8 promoter

Kunsch, C, Rosen, CA

Mol. Cell. Biol. 1993
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