scholarly journals Phosphorylation of Pal2 by the protein kinases Kin1 and Kin2 modulates HAC1 mRNA splicing in the unfolded protein response in yeast

2021 ◽  
Vol 14 (684) ◽  
pp. eaaz4401
Author(s):  
Chandrima Ghosh ◽  
Jagadeesh Kumar Uppala ◽  
Leena Sathe ◽  
Charlotte I. Hammond ◽  
Ashish Anshu ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Protein Kinases ◽  
Cellular Stress ◽  
Mrna Processing ◽  
Mrna Splicing ◽  
Cellular Stress Response ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Er Homeostasis

During cellular stress in the budding yeast Saccharomyces cerevisiae, an endoplasmic reticulum (ER)–resident dual kinase and RNase Ire1 splices an intron from HAC1 mRNA in the cytosol, thereby releasing its translational block. Hac1 protein then activates an adaptive cellular stress response called the unfolded protein response (UPR) that maintains ER homeostasis. The polarity-inducing protein kinases Kin1 and Kin2 contribute to HAC1 mRNA processing. Here, we showed that an RNA-protein complex that included the endocytic proteins Pal1 and Pal2 mediated HAC1 mRNA splicing downstream of Kin1 and Kin2. We found that Pal1 and Pal2 bound to the 3′ untranslated region (3′UTR) of HAC1 mRNA, and a yeast strain lacking both Pal1 and Pal2 was deficient in HAC1 mRNA processing. We also showed that Kin1 and Kin2 directly phosphorylated Pal2, and that a nonphosphorylatable Pal2 mutant could not rescue the UPR defect in a pal1Δ pal2Δ strain. Thus, our work uncovers a Kin1/2-Pal2 signaling pathway that coordinates HAC1 mRNA processing and ER homeostasis.

scholarly journals Herpesviruses and the Unfolded Protein Response

2019 ◽  
Author(s):  
Benjamin P. Johnston ◽  
Craig McCormick
Keyword(s):  
Stress Response ◽  
Viral Replication ◽  
Unfolded Protein Response ◽  
Stress Responses ◽  
Cellular Stress ◽  
Cellular Stress Response ◽  
Negative Effects ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

Herpesviruses usurp cellular stress responses to avoid immune detection while simultaneously promoting viral replication and spread. The unfolded protein response (UPR) is an evolutionarily conserved stress response that is activated when the protein load in the ER saturates its chaperone folding capacity causing an accrual of misfolded proteins. Through translational and transcriptional reprogramming, the UPR aims to restore protein homeostasis; however, if this fails the cell undergoes apoptosis. It is commonly thought that many enveloped viruses, including herpesviruses, may activate the UPR due to saturation of the ER with nascent glycoproteins and thus these viruses may have evolved mechanisms to evade the potentially negative effects of UPR signaling. Over the past fifteen years there has been considerable effort to provide evidence that different viruses may reprogram the UPR to promote viral replication. Here we provide an overview of the molecular events of UPR activation, signaling and transcriptional outputs, and highlight key findings that demonstrate that the UPR is an important cellular stress response that herpesviruses have hijacked to facilitate persistent infection.

scholarly journals Two Distinctly Localized P-Type ATPases Collaborate to Maintain Organelle Homeostasis Required for Glycoprotein Processing and Quality Control

2002 ◽  
Vol 13 (11) ◽  
pp. 3955-3966 ◽  
Author(s):  
Shilpa Vashist ◽  
Christian G. Frank ◽  
Claude A. Jakob ◽  
Davis T.W. Ng
Keyword(s):  
Quality Control ◽  
Unfolded Protein Response ◽  
Secretory Pathway ◽  
Ion Homeostasis ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Coa Reductase ◽  
Protein Response ◽  
P Type ◽  
Er Homeostasis

Membrane transporter proteins are essential for the maintenance of cellular ion homeostasis. In the secretory pathway, the P-type ATPase family of transporters is found in every compartment and the plasma membrane. Here, we report the identification of COD1/SPF1(control of HMG-CoA reductase degradation/SPF1) through genetic strategies intended to uncover genes involved in protein maturation and endoplasmic reticulum (ER)-associated degradation (ERAD), a quality control pathway that rids misfolded proteins. Cod1p is a putative ER P-type ATPase whose expression is regulated by the unfolded protein response, a stress-inducible pathway used to monitor and maintain ER homeostasis. COD1 mutants activate the unfolded protein response and are defective in a variety of functions apart from ERAD, which further support a homeostatic role.COD1 mutants display phenotypes similar to strains lacking Pmr1p, a Ca2+/Mn2+pump that resides in the medial-Golgi. Because of its localization, the previously reported role of PMR1 in ERAD was somewhat enigmatic. A clue to their respective roles came from observations that the two genes are not generally required for ERAD. We show that the specificity is rooted in a requirement for both genes in protein-linked oligosaccharide trimming, a requisite ER modification in the degradation of some misfolded glycoproteins. Furthermore, Cod1p, like Pmr1p, is also needed for the outer chain modification of carbohydrates in the Golgi apparatus despite its ER localization. In strains deleted of both genes, these activities are nearly abolished. The presence of either protein alone, however, can support partial function for both compartments. Taken together, our results reveal an interdependent relationship between two P-type ATPases to maintain homeostasis of the organelles where they reside.

scholarly journals RTCB-1 Mediates Neuroprotection via XBP-1 mRNA Splicing in the Unfolded Protein Response Pathway

2014 ◽  
Vol 34 (48) ◽  
pp. 16076-16085 ◽  
Author(s):  
A. Ray ◽  
S. Zhang ◽  
C. Rentas ◽  
K. A. Caldwell ◽  
G. A. Caldwell
Keyword(s):  
Unfolded Protein Response ◽  
Mrna Splicing ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

Slower rescue of ER homeostasis by the unfolded protein response pathway associated with common variable immunodeficiency

2008 ◽  
Vol 45 (10) ◽  
pp. 2990-2997 ◽  
Author(s):  
Juliana S. Kuribayashi ◽  
Cíntia R. Bombardieri ◽  
Gisele V. Baracho ◽  
Júlio Aliberti ◽  
Fabiana S. Machado ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Common Variable Immunodeficiency ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Er Homeostasis ◽  
Common Variable

Cellular stress response and apoptosis in cancer therapy

Blood ◽  
2001 ◽  
Vol 98 (9) ◽  
pp. 2603-2614 ◽  
Author(s):  
Ingrid Herr ◽  
Klaus-Michael Debatin
Keyword(s):  
Stress Response ◽  
Proteolytic Enzymes ◽  
Cellular Stress ◽  
Nuclear Factor Κb ◽  
Cellular Stress Response ◽  
Unfolded Protein ◽  
Anticancer Treatment ◽  
Mediate Cell ◽  
The Unfolded Protein Response ◽  
Protein Response

Abstract Anticancer treatment using cytotoxic drugs is considered to mediate cell death by activating key elements of the apoptosis program and the cellular stress response. While proteolytic enzymes (caspases) serve as main effectors of apoptosis, the mechanisms involved in activation of the caspase system are less clear. Two distinct pathways upstream of the caspase cascade have been identified. Death receptors, eg, CD95 (APO-1/Fas), trigger caspase-8, and mitochondria release apoptogenic factors (cytochrome c, Apaf-1, AIF), leading to the activation of caspase-9. The stressed endoplasmic reticulum (ER) contributes to apoptosis by the unfolded protein response pathway, which induces ER chaperones, and by the ER overload response pathway, which produces cytokines via nuclear factor-κB. Multiple other stress-inducible molecules, such as p53, JNK, AP-1, NF-κB, PKC/MAPK/ERK, and members of the sphingomyelin pathway have a profound influence on apoptosis. Understanding the complex interaction between different cellular programs provides insights into sensitivity or resistance of tumor cells and identifies molecular targets for rational therapeutic intervention strategies.

scholarly journals TM7SF3, a novel p53-regulated homeostatic factor, attenuates cellular stress and the subsequent induction of the unfolded protein response

2016 ◽  
Vol 24 (1) ◽  
pp. 132-143 ◽  
Author(s):  
Roi Isaac ◽  
Ido Goldstein ◽  
Noa Furth ◽  
Neta Zilber ◽  
Sarina Streim ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Cellular Stress ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response
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