Late phase of the endoplasmic reticulum stress response pathway is regulated by Hog1 MAP kinase.
When unfolded proteins accumulate in the endoplasmic reticulum (ER) causing ER stress, the unfolded protein response (UPR) responds rapidly to induce a transcriptional program that functions to alleviate the stress. However, under extreme conditions, when UPR activation is not sufficient to alleviate ER stress, the stress may persist long term. Very little is known about how the cell responds to persistent ER stress that is not resolved by the immediate activation of the UPR. We show that Hog1 MAP kinase becomes phosphorylated during the late stage of ER stress and helps the ER regain homeostasis. Although Hog1 is well known to function in osmotic stress and cell wall integrity pathways, we show that the activation mechanism for Hog1 during ER stress is distinct from both of these pathways. During late stage ER stress, upon phosphorylation, Hog1 translocates into the nucleus and regulates gene expression. Subsequently, Hog1 returns to the cytoplasm, where its phosphorylation levels remain high. From its cytoplasmic location, Hog1 contributes to the activation of autophagy by enhancing the stability of Atg8, a critical autophagy protein. Thus, Hog1 coordinates a multifaceted response to persistent ER stress.
Bicknell
Alicia A
AA
Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093, USA.
Tourtellotte
Joel
J
Niwa
Maho
M
D001343:Autophagy; D000071190:Autophagy-Related Protein 8 Family; D003593:Cytoplasm / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D006360:Heat-Shock Proteins / Q000737:chemistry; D020935:MAP Kinase Signaling System; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D008957:Models, Genetic; D010766:Phosphorylation; D011489:Protein Denaturation; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D056811:Unfolded Protein Response
C113757:ATG8 protein, S cerevisiae; D000071190:Autophagy-Related Protein 8 Family; C112591:HSP12 protein, S cerevisiae; D006360:Heat-Shock Proteins; D008869:Microtubule-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases
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