Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0848237 (acute stress)
 4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The high osmolarity glycerol (HOG) pathway, composed of membrane-associated osmosensors, adaptor proteins and core signaling kinases, is essential for the survival of yeast cells under hyper-osmotic stress. Here, we studied how the MAPKKK Ste11 might change its protein interaction profile during acute stress exposure, with an emphasis on the sensory system of the so-called Sho1/Msb2 signaling branch. To characterize the transience of protein-protein interactions we utilized a recently described enzymatic in vivo protein proximity assay (M-track). Accordingly, interaction signals between Ste11 and many of its signaling partners can already be detected even under basal conditions. In most cases these signals increase after stress induction. All the interactions are completely dependent on the function of the Ste11-adaptor protein Ste50. Moreover, the presence of either Msb2 or Hkr1 is necessary for observing the interaction between Ste11 and scaffolding factors such as Sho1 and Pbs2. Additional assays suggest that Msb2 is not only in close proximity to Ste11 but might function as an individual Ste11 concentrator at the plasma membrane. Our results confirm the existence of negative feedback systems targeting the protein levels of Ste11 and Msb2 and also hint at changes in the dissociation rates of intermediate signaling complexes.
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PMID:Msb2 is a Ste11 membrane concentrator required for full activation of the HOG pathway. 2568 21

RNA-binding proteins (RBPs) play a major role during control of mRNA localization, stability, and translation and are central to most cellular processes. In the fission yeast Schizosaccharomyces pombe, the multiple K homology (KH) domain RBP Rnc1 downregulates the activity of the cell integrity pathway (CIP) via stabilization of pmp1 + mRNA, which encodes the Pmp1 phosphatase that inactivates Pmk1, the mitogen-activated protein kinase (MAPK) component of this signaling cascade. However, Rnc1 likely regulates the half-life/stability of additional mRNAs. We show that Rnc1 downregulates the activity of Sty1, the MAPK of the stress-activated MAPK pathway (SAPK), during control of cell length at division and recovery in response to acute stress. Importantly, this control strictly depends on Rnc1's ability to bind mRNAs encoding activators (Wak1 MAPKKK, Wis1 MAPKK) and downregulators (Atf1 transcription factor, Pyp1 and Pyp2 phosphatases) of Sty1 phosphorylation through its KH domains. Moreover, Sty1 is responsible for Rnc1 phosphorylation in vivo at multiple phosphosites during growth and stress, and these modifications trigger Rnc1 for proper binding and destabilization of the above mRNA targets. Phosphorylation by Sty1 prompts Rnc1-dependent mRNA destabilization to negatively control SAPK signaling, thus revealing an additional feedback mechanism that allows precise tuning of MAPK activity during unperturbed cell growth and stress.IMPORTANCE Control of mRNA localization, stability, turnover, and translation by RNA-binding proteins (RBPs) influences essential processes in all eukaryotes, including signaling by mitogen-activated protein kinase (MAPK) pathways. We describe that in the fission yeast Schizosaccharomyces pombe the RBP Rnc1 negatively regulates cell length at division during unperturbed growth and recovery after acute stress by reducing the activity of the MAPK Sty1, which regulates cell growth and differentiation during environmental cues. This mechanism relies on Rnc1 binding to specific mRNAs encoding both enhancers and negative regulators of Sty1 activity. Remarkably, multiple phosphorylation of Rnc1 by Sty1 favors RBP binding and destabilization of the above mRNAs. Thus, posttranscriptional modulation of MAP kinase signaling by RNA-binding proteins emerges as a major regulatory mechanism that dictates the growth cycle and cellular adaptation in response to the changing environment in eukaryotic organisms.
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PMID:RNA-Binding Protein Rnc1 Regulates Cell Length at Division and Acute Stress Response in Fission Yeast through Negative Feedback Modulation of the Stress-Activated Mitogen-Activated Protein Kinase Pathway. 3191 90