Senescence-Associated Secretory Phenotype (SASP)

Acosta JC, Banito A, Wuestefeld T, Georgilis A, Janich P, Morton JP, Athineos D, Kang TW, Lasitschka F, Andrulis M, Pascual G, Morris KJ, Khan S, Jin H, Dharmalingam G, Snijders AP, Carroll T, Capper D, Pritchard C, Inman GJ, Longerich T, Sansom OJ, Benitah SA, Zender L, Gil J. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol. 2013 Aug;15(8):978–90. PMID: 23770676; PMCID: PMC3732483.; 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. DNA damage signaling triggers degradation of histone methyltransferases through APC/C(Cdh1) in senescent cells. Mol Cell. 2012 Jan 13;45(1):123–31. doi: 10.1016/j.molcel.2011.10.018. PMID: 22178396.; Chien Y, Scuoppo C, Wang X, Fang X, Balgley B, Bolden JE, Premsrirut P, Luo W, Chicas A, Lee CS, Kogan SC, Lowe SW. Control of the senescence-associated secretory phenotype by NF-?B promotes senescence and enhances chemosensitivity. Genes Dev. 2011 Oct 15;25(20):2125–36. PMID: 21979375; PMCID: PMC3205583.; Atwood AA, Sealy LJ. C/EBPß's role in determining Ras-induced senescence or transformation. Small GTPases. 2011 Jan;2(1):41–6. PMID: 21686281; PMCID: PMC3116617.; Atwood AA, Sealy L. Regulation of C/EBPbeta1 by Ras in mammary epithelial cells and the role of C/EBPbeta1 in oncogene-induced senescence. Oncogene. 2010 Nov 11;29(45):6004–15. PMID: 20818427; PMCID: PMC2978746.; Lee S, Shuman JD, Guszczynski T, Sakchaisri K, Sebastian T, Copeland TD, Miller M, Cohen MS, Taunton J, Smart RC, Xiao Z, Yu L, Veenstra TD, Johnson PF. RSK-Mediated Phosphorylation in the C/EBPß Leucine Zipper Regulates DNA Binding, Dimerization, and Growth Arrest Activity. Molecular and Cellular Biology. 2010 Jun 01;30(11):2621–35. doi: 10.1128/mcb.00782-09.; Orjalo AV, Bhaumik D, Gengler BK, Scott GK, Campisi J. Cell surface-bound IL-1alpha is an upstream regulator of the senescence-associated IL-6/IL-8 cytokine network. Proc Natl Acad Sci U S A. 2009 Oct 06;106(40):17031–6. PMID: 19805069; PMCID: PMC2761322.; Rodier F, Coppé JP, Patil CK, Hoeijmakers WA, Muñoz DP, Raza SR, Freund A, Campeau E, Davalos AR, Campisi J. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat Cell Biol. 2009 Aug;11(8):973–9. PMID: 19597488; PMCID: PMC2743561.; Young ARJ, Narita M. SASP reflects senescence. EMBO Reports. 2009 Feb 13;10(3):228–30. doi: 10.1038/embor.2009.22.; Coppé JP, Patil CK, Rodier F, Sun Y, Muñoz DP, Goldstein J, Nelson PS, Desprez PY, Campisi J. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 2008 Dec 02;6(12):2853–68. PMID: 19053174; PMCID: PMC2592359.; 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. Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell. 2008 Jun 13;133(6):1006–18. doi: 10.1016/j.cell.2008.03.038. PMID: 18555777.; Kuilman T, Michaloglou C, Vredeveld LC, Douma S, van Doorn R, Desmet CJ, Aarden LA, Mooi WJ, Peeper DS. Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell. 2008 Jun 13;133(6):1019–31. doi: 10.1016/j.cell.2008.03.039. PMID: 18555778.; Hartupee J, Li X, Hamilton T. Interleukin 1a-induced NF?B Activation and Chemokine mRNA Stabilization Diverge at IRAK1. Journal of Biological Chemistry. 2008 Jun;283(23):15689–93. doi: 10.1074/jbc.m801346200.; Wajapeyee N, Serra RW, Zhu X, Mahalingam M, Green MR. Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell. 2008 Feb 08;132(3):363–74. PMID: 18267069; PMCID: PMC2266096.; Niehof M, Streetz K, Rakemann T, Bischoff SC, Manns MP, Horn F, Trautwein C. Interleukin-6-induced tethering of STAT3 to the LAP/C/EBPbeta promoter suggests a new mechanism of transcriptional regulation by STAT3. J Biol Chem. 2001 Mar 23;276(12):9016–27. doi: 10.1074/jbc.m009284200. PMID: 11114305.; Bailly S, Fay M, Israël N, Gougerot-Pocidalo MA. The transcription factor AP-1 binds to the human interleukin 1 alpha promoter. Eur Cytokine Netw. 1996 Apr;7(2):125–8. PMID: 8688489.; Jimi E, Ikebe T, Takahashi N, Hirata M, Suda T, Koga T. Interleukin-1 alpha activates an NF-kappaB-like factor in osteoclast-like cells. J Biol Chem. 1996 Mar 01;271(9):4605–8. doi: 10.1074/jbc.271.9.4605. PMID: 8617720.; Matsusaka T, Fujikawa K, Nishio Y, Mukaida N, Matsushima K, Kishimoto T, Akira S. Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8. Proc. Natl. Acad. Sci. U.S.A. 1993 Nov;90(21):10193–7. doi: 10.1073/pnas.90.21.10193.; Nakajima T, Kinoshita S, Sasagawa T, Sasaki K, Naruto M, Kishimoto T, Akira S. Phosphorylation at threonine-235 by a ras-dependent mitogen-activated protein kinase cascade is essential for transcription factor NF-IL6. Proc. Natl. Acad. Sci. U.S.A. 1993 Mar 15;90(6):2207–11. doi: 10.1073/pnas.90.6.2207.

Metabolites

ATP(4-)

Formula: C10H12N5O13P3 (502.9644492)

CAS ID:

ADP(3-)

Formula: C10H12N5O10P2 (424.0059412)

CAS ID:



Enzyme

EC Number name full name note
2.3.2.23 E2 ubiquitin-conjugating enzyme S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine:[E2 ubiquitin-conjugating enzyme] ubiquitinyl transferase
2.3.2.24 (E3-independent) E2 ubiquitin-conjugating enzyme S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine:L-lysine ubiquitinyl transferase ([E3 ubiquitin transferase]-independent)
2.7.11.22 cyclin-dependent kinase ATP:cyclin phosphotransferase
2.7.11.24 mitogen-activated protein kinase ATP:protein phosphotransferase (MAPKK-activated)


Proteins

Protein ID name full name