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. 2013 Apr 18;5(4):683–702. doi: 10.3390/toxins5040683

Figure 2.

Figure 2

A model for transcriptional activation of antioxidant and aflatoxin biosynthetic genes by oxidative stress-related transcription factors. Based on available experimental evidence, the model proposes that increased levels of intracellular reactive oxygen species (ROS) in fungal cells down-regulate the cAMP-PKA signaling pathway. This promotes MsnA binding to STRE sites in promoters of antioxidant genes for their activation. Simultaneously, ROS up-regulate the stress activated protein kinase/mitogen activated protein kinase (SAPK/MAPK) signaling cascades through the multistep phosphorelay system. Activation of the SAPK/MAPK cascade promotes AtfB and SrrA binding (SrrA recruits AP-1) to corresponding CRE, SRRA, and AP1 sites in promoters of the antioxidant genes for their induction. Then MsnA, AtfB, and SrrA bind (SrrA recruits AP-1) to corresponding STRE, CRE, SRRA, and AP1 sites in promoters of aflatoxin genes for their activation due to excessive levels of ROS. AflR assists in induction of aflatoxin biosynthetic genes by binding to AFLR sites in the aflatoxin gene promoters. The dotted arrows indicate signal transduction from ROS and the solid lined arrows indicate signal transduction pathways. The curved arrows designate entering of transcription factors from cytoplasm to nucleus and binding of the transcription factors to the corresponding recognition motifs. Undefined yet signal transduction between MsnA and SAPK/MAPK module is shown by a question mark. PKA, protein kinase A; MP, multistep phosphorelay; SAPK/MAPK, stress activated protein kinase/mitogen activated protein kinase.