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Global Reprogramming of Host SUMOylation during Influenza Virus Infection.

Domingues P, Golebiowski F, Tatham MH, Lopes AM, Taggart A, Hay RT, Hale BG - Cell Rep (2015)

Bottom Line: This is paralleled by widespread host deSUMOylation.Depletion screening identified ten virus-induced SUMO targets as potential antiviral factors, including C18orf25 and the SMC5/6 and PAF1 complexes.Mechanistic studies further uncovered a role for SUMOylation of the PAF1 complex component, parafibromin (CDC73), in potentiating antiviral gene expression.

View Article: PubMed Central - PubMed

Affiliation: MRC-University of Glasgow Centre for Virus Research, Garscube Campus, 464 Bearsden Road, Glasgow G61 1QH, UK.

No MeSH data available.


Related in: MedlinePlus

The IAV-Induced Host SUMOylation Response Is Quantitatively Distinct from that Induced by Other Stresses(A) Quantitative SUMO2 proteomics of the heat shock response in A549s. The indicated A549s were grown for five to six cell doublings in light (L; isotopically normal, K0R0), medium (M; K4R6), or heavy (H; K8R10) SILAC medium prior to treatment (for 30 min) as indicated. Subsequent TAP purification and analyses were performed as for Figure 3. Graph shows tsMAP of SUMO2 substrates after data filtering, indicating log2-fold changes in protein modification following heat shock (y axis).(B–F) Correlations show log2-fold changes in SUMO2 modification in response to heat shock between HeLa and A549 cells (B); between IAV infection and heat shock in A549 cells (C); between IAV infection in A549 cells and proteasome inhibition (MG132) in HeLa cells (D); between IAV infection in A549 cells and Shigella flexneri infection in HeLa cells (E); and between IAV infection in A549 cells and ionizing radiation (IR; 15 Gy) in HeLa cells (F). See also Figure S5 and Table S5.
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fig5: The IAV-Induced Host SUMOylation Response Is Quantitatively Distinct from that Induced by Other Stresses(A) Quantitative SUMO2 proteomics of the heat shock response in A549s. The indicated A549s were grown for five to six cell doublings in light (L; isotopically normal, K0R0), medium (M; K4R6), or heavy (H; K8R10) SILAC medium prior to treatment (for 30 min) as indicated. Subsequent TAP purification and analyses were performed as for Figure 3. Graph shows tsMAP of SUMO2 substrates after data filtering, indicating log2-fold changes in protein modification following heat shock (y axis).(B–F) Correlations show log2-fold changes in SUMO2 modification in response to heat shock between HeLa and A549 cells (B); between IAV infection and heat shock in A549 cells (C); between IAV infection in A549 cells and proteasome inhibition (MG132) in HeLa cells (D); between IAV infection in A549 cells and Shigella flexneri infection in HeLa cells (E); and between IAV infection in A549 cells and ionizing radiation (IR; 15 Gy) in HeLa cells (F). See also Figure S5 and Table S5.

Mentions: A multitude of stresses has been demonstrated to modulate cellular SUMO modification dynamics, including heat shock, ionizing radiation, proteotoxicity, and bacterial infection. Strikingly, heat shock causes a global increase in total SUMO conjugates that, by western blot, appears similar to that observed with IAV infection (Figure 5A). To compare the cellular SUMOylation response to IAV with the response to heat shock treatment, we also used SILAC proteomics to determine how the SUMO2-modified proteome changes in TAP-SUMO2 A549 cells following incubation at 43°C for 30 min (Figure 5A; Table S5). Heat-shock-triggered SUMO2 conjugation changes in A549s strongly correlated with those previously determined in HeLa cells using similar methodologies (Golebiowski et al., 2009), thereby confirming the validity of our data and indicating that this cellular stress induces a cell-type-independent SUMO response (Pearson’s coefficient of 0.89, Figure 5B). Nevertheless, the IAV-triggered SUMOylation response in A549s did not quantitatively correlate with the heat shock SUMOylation response (Pearson’s coefficient of 0.43) (Figure 5C).


Global Reprogramming of Host SUMOylation during Influenza Virus Infection.

Domingues P, Golebiowski F, Tatham MH, Lopes AM, Taggart A, Hay RT, Hale BG - Cell Rep (2015)

The IAV-Induced Host SUMOylation Response Is Quantitatively Distinct from that Induced by Other Stresses(A) Quantitative SUMO2 proteomics of the heat shock response in A549s. The indicated A549s were grown for five to six cell doublings in light (L; isotopically normal, K0R0), medium (M; K4R6), or heavy (H; K8R10) SILAC medium prior to treatment (for 30 min) as indicated. Subsequent TAP purification and analyses were performed as for Figure 3. Graph shows tsMAP of SUMO2 substrates after data filtering, indicating log2-fold changes in protein modification following heat shock (y axis).(B–F) Correlations show log2-fold changes in SUMO2 modification in response to heat shock between HeLa and A549 cells (B); between IAV infection and heat shock in A549 cells (C); between IAV infection in A549 cells and proteasome inhibition (MG132) in HeLa cells (D); between IAV infection in A549 cells and Shigella flexneri infection in HeLa cells (E); and between IAV infection in A549 cells and ionizing radiation (IR; 15 Gy) in HeLa cells (F). See also Figure S5 and Table S5.
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getmorefigures.php?uid=PMC4660286&req=5

fig5: The IAV-Induced Host SUMOylation Response Is Quantitatively Distinct from that Induced by Other Stresses(A) Quantitative SUMO2 proteomics of the heat shock response in A549s. The indicated A549s were grown for five to six cell doublings in light (L; isotopically normal, K0R0), medium (M; K4R6), or heavy (H; K8R10) SILAC medium prior to treatment (for 30 min) as indicated. Subsequent TAP purification and analyses were performed as for Figure 3. Graph shows tsMAP of SUMO2 substrates after data filtering, indicating log2-fold changes in protein modification following heat shock (y axis).(B–F) Correlations show log2-fold changes in SUMO2 modification in response to heat shock between HeLa and A549 cells (B); between IAV infection and heat shock in A549 cells (C); between IAV infection in A549 cells and proteasome inhibition (MG132) in HeLa cells (D); between IAV infection in A549 cells and Shigella flexneri infection in HeLa cells (E); and between IAV infection in A549 cells and ionizing radiation (IR; 15 Gy) in HeLa cells (F). See also Figure S5 and Table S5.
Mentions: A multitude of stresses has been demonstrated to modulate cellular SUMO modification dynamics, including heat shock, ionizing radiation, proteotoxicity, and bacterial infection. Strikingly, heat shock causes a global increase in total SUMO conjugates that, by western blot, appears similar to that observed with IAV infection (Figure 5A). To compare the cellular SUMOylation response to IAV with the response to heat shock treatment, we also used SILAC proteomics to determine how the SUMO2-modified proteome changes in TAP-SUMO2 A549 cells following incubation at 43°C for 30 min (Figure 5A; Table S5). Heat-shock-triggered SUMO2 conjugation changes in A549s strongly correlated with those previously determined in HeLa cells using similar methodologies (Golebiowski et al., 2009), thereby confirming the validity of our data and indicating that this cellular stress induces a cell-type-independent SUMO response (Pearson’s coefficient of 0.89, Figure 5B). Nevertheless, the IAV-triggered SUMOylation response in A549s did not quantitatively correlate with the heat shock SUMOylation response (Pearson’s coefficient of 0.43) (Figure 5C).

Bottom Line: This is paralleled by widespread host deSUMOylation.Depletion screening identified ten virus-induced SUMO targets as potential antiviral factors, including C18orf25 and the SMC5/6 and PAF1 complexes.Mechanistic studies further uncovered a role for SUMOylation of the PAF1 complex component, parafibromin (CDC73), in potentiating antiviral gene expression.

View Article: PubMed Central - PubMed

Affiliation: MRC-University of Glasgow Centre for Virus Research, Garscube Campus, 464 Bearsden Road, Glasgow G61 1QH, UK.

No MeSH data available.


Related in: MedlinePlus