Browse > Article
http://dx.doi.org/10.5483/BMBRep.2019.52.8.273

JNK activation induced by ribotoxic stress is initiated from 80S monosomes but not polysomes  

Kim, Tae-Sung (Laboratory of Biochemistry, Division of Life Sciences, Korea University)
Kim, Hag Dong (Laboratory of Biochemistry, Division of Life Sciences, Korea University)
Park, Yong Jun (Laboratory of Biochemistry, Division of Life Sciences, Korea University)
Kong, EunBin (Laboratory of Biochemistry, Division of Life Sciences, Korea University)
Yang, Hee Woong (Laboratory of Biochemistry, Division of Life Sciences, Korea University)
Jung, Youjin (Laboratory of Biochemistry, Division of Life Sciences, Korea University)
Kim, YongJoong (Laboratory of Biochemistry, Division of Life Sciences, Korea University)
Kim, Joon (Laboratory of Biochemistry, Division of Life Sciences, Korea University)
Publication Information
BMB Reports / v.52, no.8, 2019 , pp. 502-507 More about this Journal
Abstract
Translation is a costly, but inevitable, cell maintenance process. To reduce unnecessary ATP consumption in cells, a fine-tuning mechanism is needed for both ribosome biogenesis and translation. Previous studies have suggested that the ribosome functions as a hub for many cellular signals such as ribotoxic stress response, mammalian target of rapamycin (mTOR), and ribosomal S6 kinase (RSK) signaling. Therefore, we investigated the relationship between ribosomes and mitogen-activated protein kinase (MAPK) activation under ribotoxic stress conditions and found that the activation of c-Jun N-terminal kinases (JNKs) was suppressed by ribosomal protein knockdown but that of p38 was not. In addition, we found that JNK activation is driven by the association of inactive JNK in the 80S monosomes rather than the polysomes. Overall, these data suggest that the activation of JNKs by ribotoxic stress is attributable to 80S monosomes. These 80S monosomes are active ribosomes that are ready to initiate protein translation, rather than polysomes that are already acting ribosomes involved in translation elongation.
Keywords
Deoxynivalenol; Emetine; JNK; Ribotoxic stress; 80S monosome;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Mahoney SJ, Dempsey JM and Blenis J (2009) Cell signaling in protein synthesis ribosome biogenesis and translation initiation and elongation. Prog Mol Biol Transl Sci 90, 53-107   DOI
2 Passmore LA, Schmeing TM, Maag D et al (2007) The eukaryotic translation initiation factors eIF1 and eIF1A induce an open conformation of the 40S ribosome. Mol Cell 26, 41-50   DOI
3 Ahn EH, Kim DW, Kang HW et al (2010) Transduced PEP-1-ribosomal protein S3 (rpS3) ameliorates 12-Otetradecanoylphorbol-13-acetate-induced inflammation in mice. Toxicology 276, 192-197   DOI
4 Kim SH and Kim J (2006) Reduction of invasion in human fibrosarcoma cells by ribosomal protein S3 in conjunction with Nm23-H1 and ERK. Biochim Biophys Acta 1763, 823-832   DOI
5 Wan F, Anderson DE, Barnitz RA et al (2007) Ribosomal protein S3: a KH domain subunit in NF-kappaB complexes that mediates selective gene regulation. Cell 131, 927-939   DOI
6 Kim J, Chubatsu LS, Admon A, Stahl J, Fellous R and Linn S (1995) Implication of mammalian ribosomal protein S3 in the processing of DNA damage. J Biol Chem 270, 13620-13629   DOI
7 Jung SO, Lee JY and Kim J (2001) Yeast ribosomal protein S3 has an endonuclease activity on AP DNA. Mol Cells 12, 84-90
8 Kim HD, Lee JY and Kim J (2005) Erk phosphorylates threonine 42 residue of ribosomal protein S3. Biochem Biophys Res Commun 333, 110-115   DOI
9 Kim TS, Kim HD and Kim J (2009) PKCdelta-dependent functional switch of rpS3 between translation and DNA repair. Biochim Biophys Acta 1793, 395-405   DOI
10 Lee SB, Kwon IS, Park J et al (2010) Ribosomal protein S3, a new substrate of Akt, serves as a signal mediator between neuronal apoptosis and DNA repair. J Biol Chem 285, 29457-29468   DOI
11 Kim TS, Kim HD, Shin HS and Kim J (2009) Phosphorylation status of nuclear ribosomal protein S3 is reciprocally regulated by protein kinase C{delta} and protein phosphatase 2A. J Biol Chem 284, 21201-21208   DOI
12 Iordanov MS, Pribnow D, Magun JL et al (1997) Ribotoxic stress response: activation of the stress-activated protein kinase JNK1 by inhibitors of the peptidyl transferase reaction and by sequence-specific RNA damage to the alpha-sarcin/ricin loop in the 28S rRNA. Mol Cell Biol 17, 3373-3381   DOI
13 Olombrada M, Rodriguez-Mateos M, Prieto D et al (2014) The acidic ribosomal stalk proteins are not required for the highly specific inactivation exerted by alpha-sarcin of the eukaryotic ribosome. Biochemistry 53, 1545-1547   DOI
14 Ouyang DY, Wang YY and Zheng YT (2005) Activation of c-Jun N-terminal kinases by ribotoxic stresses. Cell Mol Immunol 2, 419-425
15 Liu P, Wang YY, Qi X, Gu Q, Geng M and Li J (2013) Undecylprodigiosin induced apoptosis in P388 cancer cells is associated with its binding to ribosome. PLoS One 8, e65381   DOI
16 Bae HK and Pestka JJ (2008) Deoxynivalenol induces p38 interaction with the ribosome in monocytes and macrophages. Toxicol Sci 105, 59-66   DOI
17 Iordanov MS, Choi RJ, Ryabinina OP, Dinh TH, Bright RK and Magun BE (2002) The UV (Ribotoxic) stress response of human keratinocytes involves the unexpected uncoupling of the Ras-extracellular signal-regulated kinase signaling cascade from the activated epidermal growth factor receptor. Mol Cell Biol 22, 5380-5394   DOI
18 Lopez-Bergami P, Habelhah H, Bhoumik A, Zhang W, Wang LH and Ronai Z (2005) RACK1 mediates activation of JNK by protein kinase C [corrected]. Mol Cell 19, 309-320   DOI
19 Grollman AP (1967) Inhibitors of protein biosynthesis. II. Mode of action of anisomycin. J Biol Chem 242, 3226-3233   DOI
20 Zhou HR, He K, Landgraf J, Pan X and Pestka JJ (2014) Direct activation of ribosome-associated double-stranded RNA-dependent protein kinase (PKR) by deoxynivalenol, anisomycin and ricin: a new model for ribotoxic stress response induction. Toxins (Basel) 6, 3406-3425   DOI
21 Sampieri CL, Nuttall RK, Young DA, Goldspink D, Clark IM and Edwards DR (2008) Activation of p38 and JNK MAPK pathways abrogates requirement for new protein synthesis for phorbol ester mediated induction of select MMP and TIMP genes. Matrix Biol 27, 128-138   DOI
22 Iordanov MS, Pribnow D, Magun JL, Dinh TH, Pearson JA and Magun BE (1998) Ultraviolet radiation triggers the ribotoxic stress response in mammalian cells. J Biol Chem 273, 15794-15803   DOI
23 Kim HD, Kim TS and Kim J (2011) Aberrant ribosome biogenesis activates c-Myc and ASK1 pathways resulting in p53-dependent G1 arrest. Oncogene 30, 3317-3327   DOI
24 Schneider-Poetsch T, Ju J, Eyler DE et al (2010) Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin. Nat Chem Biol 6, 209-217   DOI
25 Wu S, Kumar KU and Kaufman RJ (1998) Identification and requirement of three ribosome binding domains in dsRNA-dependent protein kinase (PKR). Biochemistry 37, 13816-13826   DOI
26 Simsek D, Tiu GC, Flynn RA et al (2017) The Mammalian Ribo-interactome Reveals Ribosome Functional Diversity and Heterogeneity. Cell 169, 1051-1065 e18   DOI
27 Grosso S, Volta V, Vietri M, Gorrini C, Marchisio PC and Biffo S (2008) Eukaryotic ribosomes host PKC activity. Biochem Biophys Res Commun 376, 65-69   DOI
28 Bae H, Gray JS, Li M, Vines L, Kim J and Pestka JJ (2010) Hematopoietic cell kinase associates with the 40S ribosomal subunit and mediates the ribotoxic stress response to deoxynivalenol in mononuclear phagocytes. Toxicol Sci 115, 444-452   DOI
29 Sauter KA, Magun EA, Iordanov MS and Magun BE (2010) ZAK is required for doxorubicin, a novel ribotoxic stressor, to induce SAPK activation and apoptosis in HaCaT cells. Cancer Biol Ther 10, 258-266   DOI
30 Zhou HR, Lau AS and Pestka JJ (2003) Role of double-stranded RNA-activated protein kinase R (PKR) in deoxynivalenol-induced ribotoxic stress response. Toxicol Sci 74, 335-344   DOI
31 Zhou HR, Jia Q and Pestka JJ (2005) Ribotoxic stress response to the trichothecene deoxynivalenol in the macrophage involves the SRC family kinase Hck. Toxicol Sci 85, 916-926   DOI
32 Laskin JD, Heck DE and Laskin DL (2002) The ribotoxic stress response as a potential mechanism for MAP kinase activation in xenobiotic toxicity. Toxicol Sci 69, 289-291   DOI
33 Kim HD, Kim TS, Joo YJ et al (2010) RpS3 translation is repressed by interaction with its own mRNA. J Cell Biochem 110, 294-303   DOI
34 Klein S, Morimoto T and Rifkin DB (1996) Characterization of fibroblast growth factor-2 binding to ribosomes. Growth Factors 13, 219-228   DOI
35 Stolovich M, Tang H, Hornstein E et al (2002) Transduction of growth or mitogenic signals into translational activation of TOP mRNAs is fully reliant on the phosphatidylinositol 3-kinase-mediated pathway but requires neither S6K1 nor rpS6 phosphorylation. Mol Cell Biol 22, 8101-8113   DOI
36 Chauvin C, Koka V, Nouschi A et al (2014) Ribosomal protein S6 kinase activity controls the ribosome biogenesis transcriptional program. Oncogene 33, 474-483   DOI
37 Jetzt AE, Cheng JS, Li XP, Tumer NE and Cohick WS (2012) A relatively low level of ribosome depurination by mutant forms of ricin toxin A chain can trigger protein synthesis inhibition, cell signaling and apoptosis in mammalian cells. Int J Biochem Cell Biol 44, 2204-2211   DOI