Reg1 and Snf1 regulate stress‐induced relocalization of protein phosphatase‐1 to cytoplasmic granules

Schnell, Helena M.; Jochem, Marco; Micoogullari, Yagmur; Riggs, Claire L.; Ivanov, Pavel; Welsch, Hendrik; Ravindran, Rini; Anderson, Paul; Robinson, Lucy C.; Tatchell, Kelly; Hanna, John

doi:10.1111/febs.15802

Cited by 5 publications

(9 citation statements)

References 63 publications

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“…targeting to cytoplasmic granules in arsenite-stressed cells [49]. The nature of these granules has not been explored but they are reminiscent of foci with aggregated PP1 that accumulate when the function of Cdc48, Shp1, SDS22, or I3 is impaired.…”

Section: Pp1 Quality Control and Recyclingmentioning

confidence: 99%

“…Hence, I3 is a good candidate for the poly‐ubiquitination of dysfunctional PP1, leading to its proteasomal degradation. In budding yeast, I3 (Ypi1) and Cdc48 are also implicated in PP1 targeting to cytoplasmic granules in arsenite‐stressed cells [49]. The nature of these granules has not been explored but they are reminiscent of foci with aggregated PP1 that accumulate when the function of Cdc48, Shp1, SDS22, or I3 is impaired.…”

Section: Pp1 Quality Control and Recyclingmentioning

confidence: 99%

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Protein phosphatase 1: life‐course regulation by SDS22 and Inhibitor‐3

Cao

Lemaire

2021

The FEBS Journal

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Protein phosphatase 1 (PP1) is expressed in all eukaryotic cells and catalyzes a sizable fraction of protein Ser/Thr dephosphorylation events. It is tightly regulated in space and time through association with a wide array of Regulatory-Interactors-of-Protein-Phosphatase-One (RIPPOs).Suppressor-of-Dis2-number 2 (SDS22) and Inhibitor-3 (I3), which form a ternary complex with PP1, are the first two evolved and most widely expressed RIPPOs. Their deletion causes mitoticarrest phenotypes and is lethal in some organisms. The role of SDS22 and I3 in PP1 regulation has been a mystery for decades as they were independently identified as both activators and inhibitors of PP1. This conundrum has largely been solved by recent reports showing that SDS22 and I3 control multiple steps of the life course of PP1. Indeed, they contribute to (1) the stabilization and activation of newly translated PP1, (2) the translocation of PP1 to the nucleus, and (3) the storage of PP1 as a reserve for holoenzyme assembly. Preliminary evidence suggests that SDS22 and I3 may also function as scavengers of released or aged PP1 for re-use in holoenzyme assembly or proteolytical degradation, respectively. Hence, SDS22 and I3 are emerging as master regulators of the life course of PP1.

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Section: Pp1 Quality Control and Recyclingmentioning

confidence: 99%

Section: Pp1 Quality Control and Recyclingmentioning

confidence: 99%

Protein phosphatase 1: life‐course regulation by SDS22 and Inhibitor‐3

Cao

Lemaire

2021

The FEBS Journal

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“…PPP1CC is from a family of protein phosphatases known to be viral transcription regulators . APOBEC3F and PPP1CC are all known to play a role in cytoplasmic granule formation. , …”

Section: Resultsmentioning

confidence: 99%

“…43 APOBEC3F and PPP1CC are all known to play a role in cytoplasmic granule formation. 44,45 For this analysis, two siRNAs were used to target each mRNA encoding the protein of interest in human lung epithelial cells (Calu-3), and effects on viral RNA and protein expression as well as viral spread were assessed (Supplementary Figure 2). Note that our initial screening was done in Huh7 cells overexpressing ACE2, which substantially increased permissiveness to SARS-CoV-2 resulting in rapid viral spread.…”

Section: Validation Of a Subset Of Viral Rna Interactors Using Sirna ...mentioning

confidence: 99%

Defining Distinct RNA-Protein Interactomes of SARS-CoV-2 Genomic and Subgenomic RNAs

Whitworth,

Knoener,

Puray-Chavez

et al. 2023

J. Proteome Res.

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Host RNA binding proteins recognize viral RNA and play key roles in virus replication and antiviral mechanisms. SARS-CoV-2 generates a series of tiered subgenomic RNAs (sgRNAs), each encoding distinct viral protein(s) that regulate different aspects of viral replication. Here, for the first time, we demonstrate the successful isolation of SARS-CoV-2 genomic RNA and three distinct sgRNAs (N, S, and ORF8) from a single population of infected cells and characterize their protein interactomes. Over 500 protein interactors (including 260 previously unknown) were identified as associated with one or more target RNA. These included protein interactors unique to a single RNA pool and others present in multiple pools, highlighting our ability to discriminate between distinct viral RNA interactomes despite high sequence similarity. Individual interactomes indicated viral associations with cell response pathways, including regulation of cytoplasmic ribonucleoprotein granules and posttranscriptional gene silencing. We tested the significance of three protein interactors in these pathways (APOBEC3F, PPP1CC, and MSI2) using siRNA knockdowns, with several knockdowns affecting viral gene expression, most consistently PPP1CC. This study describes a new technology for high-resolution studies of SARS-CoV-2 RNA regulation and reveals a wealth of new viral RNA-associated host factors of potential functional significance to infection.

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“…A schematic diagram of Snf1 structure is presented as Figure 1. In addition to glucose deprivation, Snf1 is also activated by other stresses, including arsenite [47], selenite (glutathione oxidation), [48] sodium and lithium ion stress [49], high osmolarity [50], hydroxyurea [51], media alkalinity [52], and oxidative stress (peroxide) [50]. However, how Snf1 integrates the signals from these stresses has not yet been elucidated.…”

Section: Snf1 Structurementioning

confidence: 99%

Glucose Inhibits Yeast AMPK (Snf1) by Three Independent Mechanisms

Simpson-Lavy

Kupiec

2023

Biology

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Snf1, the fungal homologue of mammalian AMP-dependent kinase (AMPK), is a key protein kinase coordinating the response of cells to a shortage of glucose. In fungi, the response is to activate respiratory gene expression and metabolism. The major regulation of Snf1 activity has been extensively investigated: In the absence of glucose, it becomes activated by phosphorylation of its threonine at position 210. This modification can be erased by phosphatases when glucose is restored. In the past decade, two additional independent mechanisms of Snf1 regulation have been elucidated. In response to glucose (or, surprisingly, also to DNA damage), Snf1 is SUMOylated by Mms21 at lysine 549. This inactivates Snf1 and leads to Snf1 degradation. More recently, glucose-induced proton export has been found to result in Snf1 inhibition via a polyhistidine tract (13 consecutive histidine residues) at the N-terminus of the Snf1 protein. Interestingly, the polyhistidine tract plays also a central role in the response to iron scarcity. This review will present some of the glucose-sensing mechanisms of S. cerevisiae, how they interact, and how their interplay results in Snf1 inhibition by three different, and independent, mechanisms.

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Reg1 and Snf1 regulate stress‐induced relocalization of protein phosphatase‐1 to cytoplasmic granules

Cited by 5 publications

References 63 publications

Protein phosphatase 1: life‐course regulation by SDS22 and Inhibitor‐3

Protein phosphatase 1: life‐course regulation by SDS22 and Inhibitor‐3

Defining Distinct RNA-Protein Interactomes of SARS-CoV-2 Genomic and Subgenomic RNAs

Glucose Inhibits Yeast AMPK (Snf1) by Three Independent Mechanisms

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