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. 2020 Sep 10;23(10):101550. doi: 10.1016/j.isci.2020.101550

Fasnall Induces Atypically Transient Stress Granules Independently of FASN Inhibition

Triana Amen 1, Daniel Kaganovich 1,2,3,∗
PMCID: PMC7516299  PMID: 33083719

Summary

Stress Granule formation has been linked to the resistance of some cancer cells to chemotherapeutic intervention. A number of studies have proposed that certain anti-tumor compounds promote cancer cell survival by inducing Stress Granule formation, leading to increased cellular fitness and apoptosis avoidance. Here we show that a potent fatty acid synthase inhibitor, fasnall, known for its anti-tumor capabilities, triggers the formation of atypical Stress Granules, independently of fatty acid synthase inhibition, characterized by high internal mobility and rapid turnover.

Subject Areas: Biomolecules, Cell Biology, Cancer

Graphical Abstract

graphic file with name fx1.jpg

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Highlights

  • •

    Stress Granules can have different physical properties and clearance rates

  • •

    Fasnall induces Stress Granule formation

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    Fasnall-induced Stress Granules have increased dynamics

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    Fasnall-induced Stress Granules form independently of FASN inhibition

Biomolecules; Cell Biology; Cancer

Introduction

Stress Granules (SGs) are membraneless ribonucleoprotein compartments that form transiently during stress in most cell types ranging from yeast and plants to mammals (Kedersha and Anderson, 2002; Buchan et al., 2011; Buchan and Parker, 2009). SGs contain stalled pre-initiation complexes and RNA-binding proteins, such as TDP43, FUS, and kinases (Protter and Parker, 2016; Buchan and Parker, 2009; Walker et al., 2013; Lenzi et al., 2015). Among their many proposed functions, they are thought to serve as signaling hubs during stress conditions, regulating apoptosis, production of reactive oxygen species, nucleocytoplasmic transport, kinase signaling, and other vital cellular functions (Buchan and Parker, 2009; Kedersha and Anderson, 2007; Takahara and Maeda, 2012; Arimoto et al., 2008; Takahashi et al., 2013; Zhang et al., 2018; Thedieck et al., 2013; Amen and Kaganovich, 2020; Kaganovich, 2017). Indeed, key signaling factors, like protein kinase C, and mTORC1 components localize to SGs (Amen and Kaganovich, 2020; Fournier et al., 2013; Jevtov et al., 2015; Sfakianos et al., 2018; Thedieck et al., 2013; Kobayashi et al., 2012). SG formation and composition are fine-tuned in accordance with the specific type of stress (Aditi Mason et al., 2019; Heberle et al., 2019; Jevtov et al., 2015; Kobayashi et al., 2012; Buchan et al., 2011). It is becoming increasingly clear that precise regulation of SG composition and physical properties is critical for its cellular function (Dewey et al., 2012; Mateju et al., 2017; Patel et al., 2015; Aulas et al., 2017). For example, aberrant aggregation in SGs is implicated in the cellular pathology of amyotrophic lateral sclerosis, an age-related neurodegenerative disorder (Patel et al., 2015; Li et al., 2013; Wolozin and Ivanov, 2019).

Recent work has identified an important role for SGs in cancer. SGs incorporate multiple proteins involved in tumorogenesis, and SG components are often aberrantly expressed or mutated in cancers (Choi et al., 2019; Protter and Parker, 2016). In addition, chemotherapeutic drugs, such as bortezomib, lapatinib, and 5-fluorouracil, have been shown to induce SG formation (Adjibade et al., 2020; Kaehler et al., 2014; Anderson et al., 2015; Fournier et al., 2010). Furthermore, a link between cancer progression and SG formation is beginning to emerge. For example, several important studies have shown that SG formation promotes cancer cell survival (Choi et al., 2019; El-Naggar and Sorensen, 2018). In particular, SGs have been shown to increase cellular fitness in KRAS cancer cell lines, possibly also protecting cells from chemotherapeutic interventions (Grabocka and Bar-Sagi, 2016; Anderson et al., 2015). SGs have also been shown to protect cells from apoptosis, reducing the amount of reactive oxygen species (Thedieck et al., 2013; Takahashi et al., 2013). Inhibition of SG formation sensitizes cancer cells to anti-tumor drugs (Timalsina et al., 2018). Important questions, however, remain unanswered. It is not clear, for instance, how SG-associated downregulation of mTORC1 activity and the subsequent reduction in protein biosynthesis can be reconciled with other hallmarks of cancer, such as evading growth suppression, hyperactive proliferation, and abundant protein synthesis (Anderson et al., 2015). On the other hand, some conditions, such as selenite treatment, lead to the formation of “non-canonical” SGs with pro-apoptotic effects due to a translation block initiated from eIF4F complex formation inhibition (Fujimura et al., 2012). Other small molecules that inhibit translation initiation through eIF4A-eIF4F assembly, including pateamine A, silvestrol, and hippuristanol, also induce “non-canonical” SG assembly and have similar pro-apoptotic effects on cancer cells (Bordeleau et al., 2006; Low et al., 2005; Cencic and Pelletier, 2016; Chen et al., 2016; Kogure et al., 2013; Patton et al., 2015; Dang et al., 2006; Slaine et al., 2017; Mazroui et al., 2006). Therefore, to develop a clear understanding of the mode of action of SG, it is important to identify the trigger-specific differences in their assembly, dynamics, and composition.

Our data identify an anti-tumor compound that triggers SG formation. We show that a potent fatty acid synthase (FASN) inhibitor and anti-tumor reagent (Alwarawrah et al., 2016), fasnall, induces SG formation in human cells. We demonstrate that fasnall-induced SGs have higher internal dynamics, faster clearance kinetics, and slightly different composition than SGs induced by arsenite treatment. Finally, we show that fasnall induces SG formation independently of its FASN inhibition activity.

Results

Fasnall Induces Stress Granule Formation

We identified fasnall in the screen for PABPC1 inclusion formation. PABPC1 is a major component of SGs (Aulas et al., 2017; Jain et al., 2016), thus we set out to determine whether these granules are, in fact, SGs. First, we confirmed that PABPC1-positive inclusions harbor other SG markers, G3BP and TIA1, by immunofluorescence in the endogenously tagged PABPC1 human cell line, and in an independent cell line without fluorescent tags (Figures 1A and S1A). The timeline of SG formation was similar to that of arsenite-induced SGs (Figure 1B), with the majority of HEK293T cells forming SGs after 1 h of treatment (Figure 1B). However, SG formation was delayed in HeLa cells (Figure S1B) and the clearance time was markedly different. Fasnall-induced SGs cleared in 15 min, whereas arsenite-induced SGs needed almost 4 times as much time to clear (Figures 1C and S1C) (Wheeler et al., 2016). However, both arsenite and fasnall-induced SGs exhibited a slight increase in size at the beginning of the recovery (Figures 1C and S1F). Inhibition of polysome disassembly by cycloheximide is known to inhibit SG formation (Mollet et al., 2008), and addition of cycloheximide to fasnall prevented SG formation as well (Figures 1D and S1G). Next, we assessed eIF2 phosphorylation at the Ser51, a marker for arsenite-induced SGs (Rabouw et al., 2020). Fasnall did not induce phosphorylation, as opposed to arsenite treatment (Figures 1E and S2A). Not surprisingly, fasnall also did not induce a significant reduction in the translation (Figure 1F), as assessed by FAM-dC-puromycin incorporation (Starck et al., 2004).

Figure 1.

Figure 1

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Fasnall Induces Stress Granule Formation

(A) Immunofluorescence of SG markers during fasnall treatment. PABPC1-DDR2 HEK293T cells were treated with fasnall (50 μM) for 1 h. Cells were fixed and stained with anti-TIA1 and anti-G3BP antibodies. Hoechst (10 μg/mL) was used to stain the nucleus 30 min before imaging. Confocal planes are shown; scale bar, 5 μm.

(B) Timeline of SG formation in fasnall and arsenite conditions. HEK293T cells expressing endogenously tagged PABPC1-DDR2 were treated with arsenite (100 μM) or fasnall (50 μM) for indicated amounts of time. Representative confocal images are shown; scale bar, 5 μm. Arrowheads indicate SGs.

(C) Timeline of SG formation and clearance in HEK293T cells expressing PABPC1-DDR2 during fasnall (100 μM) and arsenite (200 μM) treatment for 1 h followed by 1 h of recovery (cells were washed 3 times with the control media). Graph represents average SG size, n = 30. Refer to Figures S1C and S1G.

(D) Confocal microscopy of SG formation in HEK293T cells expressing PABPC1-DDR2 during fasnall (50 μM), fasnall and cycloheximide (10 μg/mL, simultaneous addition), arsenite (100 μM), and arsenite and cycloheximide 1-h treatments; scale bar, 5 μm. (see also Figure S1G for quantification).

(E) Western blot of eIF2 phosphorylation on Ser51 in HELA and HEK293T cell lysates. Cells were treated with fasnall (100 μM, 1 h or 24 h) or arsenite (100 μM, 1 h) before lysis; ∗ - p<0.01. (see also Figure S2A for quantification)

(F) Puromycin incorporation assay. Graph shows average fluorescence intensity of FAM-dC-puromycin in the cytoplasm of the HEK293T cells treated with fasnall (100 μM), arsetnie (100 μM), or cycloheximide for 6 h, n = 30; p values relative to control are indicated above the graph.

(G) Schematic of protein identification by liquid chromatography-tandem mass spectrometry. HE293T cells expressing PABPC1 fused to promiscuous biotin ligase BirA (R118G) and GFP were subjected to arsenite or fasnall (100 μM each) with addition of biotin for 6 h after 1 h of treatment. Cells were lysed, and biotinylated proteins were captured on magnetic beads, followed by on-bead digestion and MS.

(H) Fluorescence intensity profile of biotinylated protein enrichment in an SG during fasnall treatment (100 μM). See also Figure S1D for the corresponding images.

(I) Venn diagram of PABPC1 interactors after control subtraction (only hits present in SG conditions and not in control conditions) in different conditions.

(J) Gene ontology (GO) analysis of SG-enriched proteins (hits enriched in SG conditions comparing to control conditions) grouped by conditions. Shown annotations are significantly enriched and hierarchically arranged. Analysis is performed by STRING web tool (https://string-db.org/).

(K) Analysis of SG-enriched fraction by comparison with TDP43-interacting proteins (Freibaum et al., 2010); overlap with the G3BP SG fraction indicated in blue (Markmiller et al., 2017).

SGs are multiprotein granules that potentially consist of over a hundred different proteins (Jain et al., 2016). We asked whether the SG proteome in fasnall conditions is similar to the proteome of SGs that form in response to arsenite treatment, a commonly used SG trigger (Lu et al., 2001) (Figure 1G). This was done using the proteomic BioID approach (Roux et al., 2013), which entailed expressing PABPC1-BirA (R118G)-GFP resulting in proximity-associated biotinylation of PABPC1-interacting proteins, and subsequent subtraction of control condition hits allows identification of SG and SG-interacting proteins (Figure 1G). We confirmed that biotinylated proteins are present in SGs (Figures 1H, S1D, and S1I). We identified 256 PABPC1 proximal proteins in fasnall conditions. After subtraction of proteins present in control conditions, 86 proteins remained, 40 of which were overlapping with interactors from arsenite-treated group (Figure 1I and Table S1). Gene ontology of SG-enriched proteins shows a similar pattern of protein distribution, indicating that SGs are similar in all conditions (Figure 1J). Eighteen proteins overlapped with the interactome of another SG component, TDP43 (Freibaum et al., 2010), and two of them were previously identified in the G3BP SG interactome (Markmiller et al., 2018) (Figures 1K, S1J, and S1K).

Fasnall Induces Stress Granules Independent of FASN

Fasnall is a selective FASN inhibitor (Alwarawrah et al., 2016). FASN is a cytoplasmic enzyme essential for de novo fatty acid synthesis and can potentially be sequestered in SGs during stress. Interestingly, FASN was proximal to PABPC1 in arsenite conditions (Table S1). First, we looked at FASN localization during SG formation and determined that FASN is not a part of SGs by immunofluorescence microscopy in arsenite and fasnall conditions (Figures 2A and 2B). If SG formation is dependent on the inhibition of FASN, then other small molecules inhibiting the enzyme would be expected to induce SGs as well. We tested another FASN inhibitor, C75, which failed to induce SG formation at a similar concentration (100 μM) (Figures 2C and 2D). To understand the role that FASN inhibition plays in fasnall-induced SG formation we created an FASN knockout using CRISPR/Cas9 (Figures 2E, S1E, and S2B). Interestingly, SG formed to the same extent in the knockout (and hence, independently of FASN availability) (Figures 2F and 2G), indicating that there fasnall exerts additional effects on the cell that are independent of FASN inhibition.

Figure 2.

Figure 2

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Fasnall Induces SGs Independent of FASN

(A) Immunofluorescence of FASN during SG formation. HEK293T cells expressing endogenously tagged PABPC1-DDR2 were treated with fasnall (50 μM) or arsenite for 1 h. Cells were fixed and stained with anti-FASN antibody. Hoechst (10 μg/mL) was used to stain the nucleus 30 min before imaging. Co-localization coefficient between FASN and PABPC1 is shown in the top right corner of the merged images. Representative confocal planes are shown; scale bar, 5 μm.

(B) Fluorescence intensity profile of FASN and PABPC1 enrichment in an SG during fasnall treatment (100 μM).

(C and D) SG formation in fasnall, C75, and arsenite conditions. HEK293T cells expressing PABPC1-DDR2 were treated with fasnall (50 μM), arsenite (100 μM), and C75 (100 μM) for 1 h. (C) Quantification of the ratio of cells with SGs in the population; mean ± SEM; the ratios (n = 3) were pooled from 300 cells, p < 0.01. (D) Representative confocal images are shown; scale bar, 5 μm.

(E) Confirmation of CRISPR/Cas9 knockout (KO) of FASN. Control and FASN KO HEK293T clonal populations were grown to 90% confluency, lysed, and analyzed by western blot. Quantification shows the ratio of FASN to GAPDH. See also Figure S2B.

(F and G) Analysis of Stress Granule formation in control and FASN KO cells. HEK293T WT and FASN KO cells were treated with arsenite (100 μM) or fasnall (50 μM) for 1 h and then fixed and stained with anti-FASN and anti-TIA antibodies (SG marker). (F) Quantification of the ratio of cells with SGs in the population; mean ± SEM, non-significant differences; the ratios (n = 3) were pooled from 300 cells. (G) Representative confocal planes are shown; scale bar, 5 μm.

Fasnall-Induced Stress Granules Have Higher Internal Mobility

As noted earlier, fasnall-induced SGs had a markedly different PABPC1 interactome than arsenite-induced SGs. There was, however, another noticeable difference: the majority of fasnall-induced SGs were rounder in shape than arsenite-induced SGs (Figure 3A). To quantify this parameter, we obtained the ratio between the maximal size of the longest (L) side and the side perpendicular to it (S) of single SGs formed in different conditions. Indeed, SGs in fasnall treatment exhibited a ratio closer to 1, indicative of a rounder shape (Figure 3B). SGs have liquid droplet-like properties (Khalfallah et al., 2018; Protter and Parker, 2016; Amen and Kaganovich, 2015), which can be assessed by measuring the internal dynamics of resident proteins. We hypothesized that the rounder shape of fasnall-induced SGs may indicate a more liquid-like state. To measure the internal dynamics of the major SG component PABPC1, which is present in equal concentrations in fasnall- and arsenite-induced SGs (Figures 3C and 3D), we used an endogenously tagged PABPC1-DDR2 cell line. DDR2 is a photoconvertible fluorescent protein, which switches its emission to a longer wavelength upon activation with a non-phototoxic dose of a blue laser (Gurskaya et al., 2006) (Figure 3E). This enables tracking the pool of red (photoconverted) proteins in live cells and in single SGs (Gura Sadovsky et al., 2017) (Figure 3E). We measured the internal dynamics of the largest SGs in the fasnall-induced SG population to reduce size and intensity biases when comparing the diffusion parameter. We photoconverted a small portion of a SG and tracked the red fluorescence intensity until it averaged with the SGs (Figures 3F, fasnall; 3G, arsenite). To account for size differences, we calculated averaging over the same distance that was photoconverted, rather than complete equilibration of the SG. This parameter, which we called diffusion, indicates how fast the photoconverted pool equilibrates with a similar surrounding volume in the SG. Fasnall SGs exhibited faster diffusion than arsenite SGs (Figures 3H and 3I). Together these data indicate that fasnall-induced SGs have readily discernable component and internal dynamic differences from arsenite-induced SGs.

Figure 3.

Figure 3

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Fasnall-Induced SGs have Higher Internal Mobility

(A and B) Live confocal microscopy of SGs in HEK293T cells expressing endogenously tagged PABPC1-DDR2. Representative confocal planes of single SGs are shown in fasnall and arsenite conditions; scale bar, 1 μm (5 μm for the cells). (B) Quantification shows ratio of maximal length (L) of SGs to a maximal perpendicular width (S); mean ± SEM, n = 25, ∗p < 0.05.

(C and D) Fluorescence intensity of SGs in HEK293T cells expressing endogenously tagged PABPC1-DDR2. (C) Quantification shows the average intensity of SGs in fasnall and arsenite conditions; mean ± SEM, non-significant difference, n = 100. (D) Intensity surface plot of control and SG conditions; scale bar, 5 μm.

(E) Schematic of photoconversion and example of SG photoconversion using endogenously tagged PABPC1-DDR2 HEK293T cells. Confocal planes show single SGs in live HEK293T cells during and after photoconversion; scale bar, 1 μm.

(F and G) Timeline of the fluorescence intensity profiles of a single SG during photoconversion in fasnall (F) and arsenite (G) conditions. Red graphs represent photoconverted DDR2 population.

(H and I) (H) Quantification of the photoconverted protein diffusion time inside single SGs in fasnall and arsenite conditions; mean ± SEM, n = 15, ∗p < 0.05. (I) Confocal microscopy of SG photoconversion in HEK293T cells expressing endogenously tagged PABPC1-DDR2 in fasnall and arsenite conditions. Representative confocal planes are shown; scale bar, 1 μm.

Fasnall Inhibits Growth and Induces Apoptosis

Next, we verified that Fasnall inhibits growth as it was reported previously for different cell lines (Alwarawrah et al., 2016) at a concentration that we used for SG induction (Figures 4A and 4B). Both HEK293T and HeLa cells exhibited a similar decrease in growth compared with control cells (Figures 4A and S1H). Fasnall has been shown to induce apoptosis (Alwarawrah et al., 2016), and we confirmed this in the cell lines that we used (Figures 4C and 4D). Additionally we tested growth inhibition in FASN KO cell line and found that fasnall inhibits growth in both control and knockout (Figure 4B).

Figure 4.

Figure 4

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Fasnall Inhibits Cell Growth at SG Inducing Concentrations

(A) Cell growth assessment using WST-8 assay (Cell counting kit-8, Sigma) in HeLa cells grown for 4 days in a complete media supplemented with fasnall, arsenite, or C75 at indicated concentrations; n = 6, ∗p < 0.05, see also Figure S1H.

(B) Cell growth assessment using WST-8 assay (Cell counting kit-8, Sigma) in HEK293T control and FASN KO cells grown for 3 days in a complete media supplemented with fasnall (100 μM) or C75 (100 μM), n = 6, ∗p < 0.01.

(C and D) LDH release from HELA (C) or HEK293T (D) cells treated with fasnall, arsenite, C75 for indicated amounts of time; mean ± SEM, n = 6. p Values relative to control are indicated above the graph.

Discussion

One of the hallmarks of cancer is the remarkable resilience of cancer cells (Hanahan and Weinberg, 2011). It stems from multifactorial reprogramming, including changes in cellular metabolism, protein synthesis, and stress response pathways (Hanahan and Weinberg, 2011; El-Naggar and Sorensen, 2018). SG formation as a response to chemotherapy appears to be instrumental in providing cancer cells with a platform for signaling and translational control, with an added benefit of protective functions during stress (El-Naggar and Sorensen, 2018). In other cases, however, SGs can exert pro-apoptotic effects (Fujimura et al., 2012; Reineke et al., 2018). We show that the anti-tumor drug, fasnall, induces non-canonical SG formation in different human cell lines at a concentration shown to block cancer cell proliferation and induce apoptosis (Alwarawrah et al., 2016). Although SG formation correlates with apoptosis, it is not clear if SGs exert pro- or anti-apoptotic action, Metabolic reprogramming in cancer often involves reliance on de novo fatty acid synthesis by FASN (Rohrig and Schulze, 2016; Koundouros and Poulogiannis, 2020), and inhibition of FASN by fasnall is a promising target in cancer research (Alwarawrah et al., 2016). Here we show that fasnall induces SG formation independently of FASN inhibition. Interestingly, another similar drug, the FASN inhibitor C75 (Kuhajda et al., 2000), does not trigger SG formation in the HEK293T cell line. Fasnall inhibits cancer cell proliferation and induces changes in lipid profiles, and both of these functions are related to FASN inhibition (Alwarawrah et al., 2016). Treatment with 50–100 μM (sufficient to block proliferation) triggers SG formation. It is therefore clear that SGs form not in response to FASN inhibition but to another unknown action of fasnall. Even though SGs may confer stress resilience on cancer cells through their anti-apoptotic function (Gao et al., 2019; Grabocka and Bar-Sagi, 2016), cancer cells with high reliance on protein production cannot easily benefit from a persistent SG response, and SG can have a stalling effect for cellular growth and division. Interestingly, fasnall inhibited growth of both control and FASN KO cells at SG formation concentrations. It is therefore interesting to further explore how SG formation contributes to cell-cycle arrest and to clarify the role of SGs in chemotherapy resistance (Gao et al., 2019).

The internal dynamics of SG and other membraneless compartments are implicated in disease pathology (Mann et al., 2019; Mateju et al., 2017; Patel et al., 2015; Amen and Kaganovich, 2015). Specifically, aberrant aggregation or persistence of SGs can be toxic to cells (Mann et al., 2019). We show that fasnall-induced SGs are different from canonical arsenite-induced SGs in internal dynamics and composition. The shape and liquidity of fasnall-induced SGs can indicate (1) differential association of phase-separating components (Riback, 2020) and (2) lack of external SG interactors that result in a more uniform shape of SGs. For example, a recently identified RNP granule component hnRNPF was enriched in the arsenite-induced SG interactome, but not in fasnall conditions (White et al., 2012). VCP, the regulator of autophagic clearance of SGs was also enriched in arsenite-induced but not fasnall-induced SG interactomes (Buchan et al., 2013) (Figures S1J and S1K). We also found that fasnall-induced SGs have almost four times faster clearance kinetics than those of arsenite-induced SGs, possibly due to reduced size of the fasnall-induced SGs. It is therefore interesting to further explore the differences in clearance mechanisms of fasnall-induced SGs and to investigate the protective functions of SGs in relation to the composition and dynamics of these membraneless compartments.

Limitations of the Study

In this study we found that fasnall induces SG formation. We have not demonstrated, however, if SG formation in case of fasnall plays a causative role in its pro-apoptotic activity in cancer cell lines. We show that SG formation in general correlates with increase in an apoptosis marker. However, whether SGs form to protect the cells or promote apoptosis in these conditions remains to be determined. Our data point toward the unspecific effects when utilizing relatively high concentrations of fasnall, which include SG formation and growth inhibition, and are independent of the inhibitory function of fasnall toward FASN. It would be interesting, therefore, to further examine to what extent the metabolic inhibition of FASN and the unspecific effects contribute to the toxicity.

Resource Availability

Lead Contact

Further information and requests for resources and reagents should be directed to and will be fulfilled by the Lead Contact, Daniel Kaganovich, daniel.kaganovich@med.uni-goettingen.de; dan@mail.huji.ac.il.

Materials Availability

Materials generated in this study, e.g. plasmids, will be made available on request.

Data and Code Availability

The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (Perez-Riverol et al., 2019) partner repository with the dataset identifier PXD021229. Additional data that support the conclusions of this study are available on reasonable request. This study did not generate any code.

Methods

All methods can be found in the accompanying Transparent Methods supplemental file.

Acknowledgments

We thank Christof Lenz, Lisa Neuenroth, and Thierry Wasselin at the UMG Core Facility Proteomics for obtaining MS data. William Breuer provided technical assistance with Mass Spectrometry sample preparation. This work was supported by the European Research Council under the European Union's Seventh Framework Program (FP/2007-2013)/ERC-StG2013 337713 DarkSide starting grant. The authors declare no conflicts of interest.

Author Contributions

All aspects of the work comprising the manuscript were carried out jointly by D.K. and T.A.

Declaration of Interests

The authors declare no competing interests.

Published: October 23, 2020

Footnotes

Supplemental Information can be found online at https://doi.org/10.1016/j.isci.2020.101550.

Supplemental Information

Document S1. Transparent Methods and Figures S1 and S2
mmc1.pdf (627.5KB, pdf)
Table S1. PABPC1 BioID Proteomics Results in Fasnall and Arsenite Conditions, Related to Figure 1
mmc2.xlsx (40.2KB, xlsx)

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Document S1. Transparent Methods and Figures S1 and S2
mmc1.pdf (627.5KB, pdf)
Table S1. PABPC1 BioID Proteomics Results in Fasnall and Arsenite Conditions, Related to Figure 1
mmc2.xlsx (40.2KB, xlsx)

Data Availability Statement

The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (Perez-Riverol et al., 2019) partner repository with the dataset identifier PXD021229. Additional data that support the conclusions of this study are available on reasonable request. This study did not generate any code.

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