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. Author manuscript; available in PMC: 2020 Dec 1.
Published in final edited form as: Eur J Cell Biol. 2019 May 21;98(5-8):151043. doi: 10.1016/j.ejcb.2019.05.002

Figure 5. Hypothetical Conserved Pathway for MANF-1 regulation of IRE-1 bifurcation.

Figure 5.

ER stress activates the regulators of UPR (atf-6, ire-1 and pek-1) and the data presented herein support a role for manf-1 in the regulation of the ire-1 arm of the unfolded protein response (UPR) by acting as both a negative regulator of xbp-1 transcriptional activation and a positive regulator of innate immunity factors in response to tunicamycin.m. ER stress and protein misfolding activate the ire-1 pathway by dissociating hsp-3/4 from ire-1 allowing ire-1 to become phosphorylate (yellow circles) leading to activation of xbp-1 as well as of other transcriptional factors. We also suggest a conserved feedback loop whereby ER stress and xbp-1 activation results in increased manf-1 expression (as also reported in mammalian cell culture (Wang et al., 2018)), suppressing further xbp-1 activation and acting as a negative regulator of the UPR.