Ribotoxic stress response

What are the mechanisms by which trichothecenes exert their transcriptional and post-transcriptional effects The 60S ribosomal subunit is a well-known molecular target of trichothecenes in leukocytes and other actively proliferating eukaryotic cells,3 whereas attempts to demonstrate alternative receptors have not been successful.37 38 Translational inhibitors that bind to ribosomes rapidly activate mitogen-activated protein kinases (MAPKs) and apoptosis via a mechanism termed the ribotoxic stress response. 39-40... 

Iordanov, M. S. et al. 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, 1997. 

Laskin, J. D., Heck D.E., and Laskin D.L. The ribotoxic stress response as a potential mechanism for MAP kinase activation in xenobiotic toxicity. Toxicol. Sci. 69, 289, 2002. 

Shifrin, V. I. and Anderson P. Trichothecene mycotoxins trigger a ribotoxic stress response that activates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase and induces apoptosis. J. Biol. Chem. 274, 13985, 1999. 

Zhou, H. R., Lau A.S., and Pestka J.J. Role of double-stranded RNA-activated protein kinase R (PKR) in deoxynivalenol-induced ribotoxic stress response. Toxicol. Sci. 74, 335, 2003. 

PS — non-competitive 80S ribosomal 60S subunit PT, competes with Trichothecin (triggers ribotoxic stress response activating JNK1)... 

S PS, 80S PT [1], yeast ribosome binding [0.7-2 nM] PS, 80S ribosomal 60S subunit PT (triggers ribotoxic stress response activatingJNK1) [antibacterial, mycotoxin, toxic] PS - 80S ribosomal 60S subunit PT (at 10) [caspase-3 activation (at 10) apoptotic, cytotoxic]... 

Zhou, H.R., Jia, Q., Pestka, J.J. (2005b). Ribotoxic stress response to the trichothecene deoxynivalenol in the macrophage involves the SRC family kinase hck. Toxicol. Sci. 85 916-26. 

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