STEEP mediates STING ER exit and activation of signaling

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

STEEP mediates STING ER exit and activation of signaling. / Zhang, Bao-cun; Nandakumar, Ramya; Reinert, Line S.; Huang, Jinrong; Laustsen, Anders; Gao, Zong-liang; Sun, Cheng-long; Jensen, Søren Beck; Troldborg, Anne; Assil, Sonia; Berthelsen, Martin F.; Scavenius, Carsten; Zhang, Yan; Windross, Samuel J.; Olagnier, David; Prabakaran, Thaneas; Chiranjeevi, Bodda; Narita, Ryo; Cai, Yujia; Zhang, Cong-gang; Stenmark, Harald; Doucet, Christine M.; Noda, Takeshi; Guo, Zheng; Goldbach-Mansky, Raphaela; Hartmann, Rune; Chen, Zhijian J.; Enghild, Jan J.; Bak, Rasmus O.; Thomsen, Martin K.; Paludan, Søren R.

I: Nature Immunology, Bind 21, Nr. 8, 2020, s. 868-+.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Zhang, B, Nandakumar, R, Reinert, LS, Huang, J, Laustsen, A, Gao, Z, Sun, C, Jensen, SB, Troldborg, A, Assil, S, Berthelsen, MF, Scavenius, C, Zhang, Y, Windross, SJ, Olagnier, D, Prabakaran, T, Chiranjeevi, B, Narita, R, Cai, Y, Zhang, C, Stenmark, H, Doucet, CM, Noda, T, Guo, Z, Goldbach-Mansky, R, Hartmann, R, Chen, ZJ, Enghild, JJ, Bak, RO, Thomsen, MK & Paludan, SR 2020, 'STEEP mediates STING ER exit and activation of signaling', Nature Immunology, bind 21, nr. 8, s. 868-+. https://doi.org/10.1038/s41590-020-0730-5

APA

Zhang, B., Nandakumar, R., Reinert, L. S., Huang, J., Laustsen, A., Gao, Z., Sun, C., Jensen, S. B., Troldborg, A., Assil, S., Berthelsen, M. F., Scavenius, C., Zhang, Y., Windross, S. J., Olagnier, D., Prabakaran, T., Chiranjeevi, B., Narita, R., Cai, Y., ... Paludan, S. R. (2020). STEEP mediates STING ER exit and activation of signaling. Nature Immunology, 21(8), 868-+. https://doi.org/10.1038/s41590-020-0730-5

Vancouver

Zhang B, Nandakumar R, Reinert LS, Huang J, Laustsen A, Gao Z o.a. STEEP mediates STING ER exit and activation of signaling. Nature Immunology. 2020;21(8):868-+. https://doi.org/10.1038/s41590-020-0730-5

Author

Zhang, Bao-cun ; Nandakumar, Ramya ; Reinert, Line S. ; Huang, Jinrong ; Laustsen, Anders ; Gao, Zong-liang ; Sun, Cheng-long ; Jensen, Søren Beck ; Troldborg, Anne ; Assil, Sonia ; Berthelsen, Martin F. ; Scavenius, Carsten ; Zhang, Yan ; Windross, Samuel J. ; Olagnier, David ; Prabakaran, Thaneas ; Chiranjeevi, Bodda ; Narita, Ryo ; Cai, Yujia ; Zhang, Cong-gang ; Stenmark, Harald ; Doucet, Christine M. ; Noda, Takeshi ; Guo, Zheng ; Goldbach-Mansky, Raphaela ; Hartmann, Rune ; Chen, Zhijian J. ; Enghild, Jan J. ; Bak, Rasmus O. ; Thomsen, Martin K. ; Paludan, Søren R. / STEEP mediates STING ER exit and activation of signaling. I: Nature Immunology. 2020 ; Bind 21, Nr. 8. s. 868-+.

Bibtex

@article{a180cf8c68b442948b82492fbed2698d,
title = "STEEP mediates STING ER exit and activation of signaling",
abstract = "STING ER exit is the rate-limiting step in STING signaling, but the mechanism that drives this process is not understood. Paludan and colleagues identify CxORF56, called STEEP here, as a positive regulator of STING signaling.STING is essential for control of infections and for tumor immunosurveillance, but it can also drive pathological inflammation. STING resides on the endoplasmic reticulum (ER) and traffics following stimulation to the ERGIC/Golgi, where signaling occurs. Although STING ER exit is the rate-limiting step in STING signaling, the mechanism that drives this process is not understood. Here we identify STEEP as a positive regulator of STING signaling. STEEP was associated with STING and promoted trafficking from the ER. This was mediated through stimulation of phosphatidylinositol-3-phosphate (PtdIns(3)P) production and ER membrane curvature formation, thus inducing COPII-mediated ER-to-Golgi trafficking of STING. Depletion of STEEP impaired STING-driven gene expression in response to virus infection in brain tissue and in cells from patients with STING-associated diseases. Interestingly, STING gain-of-function mutants from patients interacted strongly with STEEP, leading to increased ER PtdIns(3)P levels and membrane curvature. Thus, STEEP enables STING signaling by promoting ER exit.",
keywords = "CYCLIC GMP-AMP, INNATE IMMUNITY, DNA VIRUSES, ADAPTER, TRANSLOCATION, PHOSPHORYLATION, 2ND-MESSENGER, AUTOPHAGY, SYNTHASE",
author = "Bao-cun Zhang and Ramya Nandakumar and Reinert, {Line S.} and Jinrong Huang and Anders Laustsen and Zong-liang Gao and Cheng-long Sun and Jensen, {S{\o}ren Beck} and Anne Troldborg and Sonia Assil and Berthelsen, {Martin F.} and Carsten Scavenius and Yan Zhang and Windross, {Samuel J.} and David Olagnier and Thaneas Prabakaran and Bodda Chiranjeevi and Ryo Narita and Yujia Cai and Cong-gang Zhang and Harald Stenmark and Doucet, {Christine M.} and Takeshi Noda and Zheng Guo and Raphaela Goldbach-Mansky and Rune Hartmann and Chen, {Zhijian J.} and Enghild, {Jan J.} and Bak, {Rasmus O.} and Thomsen, {Martin K.} and Paludan, {S{\o}ren R.}",
note = "Author Correction: STEEP mediates STING ER exit and activation of signaling DOI: 10.1038/s41590-020-0803-5",
year = "2020",
doi = "10.1038/s41590-020-0730-5",
language = "English",
volume = "21",
pages = "868--+",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "nature publishing group",
number = "8",

}

RIS

TY - JOUR

T1 - STEEP mediates STING ER exit and activation of signaling

AU - Zhang, Bao-cun

AU - Nandakumar, Ramya

AU - Reinert, Line S.

AU - Huang, Jinrong

AU - Laustsen, Anders

AU - Gao, Zong-liang

AU - Sun, Cheng-long

AU - Jensen, Søren Beck

AU - Troldborg, Anne

AU - Assil, Sonia

AU - Berthelsen, Martin F.

AU - Scavenius, Carsten

AU - Zhang, Yan

AU - Windross, Samuel J.

AU - Olagnier, David

AU - Prabakaran, Thaneas

AU - Chiranjeevi, Bodda

AU - Narita, Ryo

AU - Cai, Yujia

AU - Zhang, Cong-gang

AU - Stenmark, Harald

AU - Doucet, Christine M.

AU - Noda, Takeshi

AU - Guo, Zheng

AU - Goldbach-Mansky, Raphaela

AU - Hartmann, Rune

AU - Chen, Zhijian J.

AU - Enghild, Jan J.

AU - Bak, Rasmus O.

AU - Thomsen, Martin K.

AU - Paludan, Søren R.

N1 - Author Correction: STEEP mediates STING ER exit and activation of signaling DOI: 10.1038/s41590-020-0803-5

PY - 2020

Y1 - 2020

N2 - STING ER exit is the rate-limiting step in STING signaling, but the mechanism that drives this process is not understood. Paludan and colleagues identify CxORF56, called STEEP here, as a positive regulator of STING signaling.STING is essential for control of infections and for tumor immunosurveillance, but it can also drive pathological inflammation. STING resides on the endoplasmic reticulum (ER) and traffics following stimulation to the ERGIC/Golgi, where signaling occurs. Although STING ER exit is the rate-limiting step in STING signaling, the mechanism that drives this process is not understood. Here we identify STEEP as a positive regulator of STING signaling. STEEP was associated with STING and promoted trafficking from the ER. This was mediated through stimulation of phosphatidylinositol-3-phosphate (PtdIns(3)P) production and ER membrane curvature formation, thus inducing COPII-mediated ER-to-Golgi trafficking of STING. Depletion of STEEP impaired STING-driven gene expression in response to virus infection in brain tissue and in cells from patients with STING-associated diseases. Interestingly, STING gain-of-function mutants from patients interacted strongly with STEEP, leading to increased ER PtdIns(3)P levels and membrane curvature. Thus, STEEP enables STING signaling by promoting ER exit.

AB - STING ER exit is the rate-limiting step in STING signaling, but the mechanism that drives this process is not understood. Paludan and colleagues identify CxORF56, called STEEP here, as a positive regulator of STING signaling.STING is essential for control of infections and for tumor immunosurveillance, but it can also drive pathological inflammation. STING resides on the endoplasmic reticulum (ER) and traffics following stimulation to the ERGIC/Golgi, where signaling occurs. Although STING ER exit is the rate-limiting step in STING signaling, the mechanism that drives this process is not understood. Here we identify STEEP as a positive regulator of STING signaling. STEEP was associated with STING and promoted trafficking from the ER. This was mediated through stimulation of phosphatidylinositol-3-phosphate (PtdIns(3)P) production and ER membrane curvature formation, thus inducing COPII-mediated ER-to-Golgi trafficking of STING. Depletion of STEEP impaired STING-driven gene expression in response to virus infection in brain tissue and in cells from patients with STING-associated diseases. Interestingly, STING gain-of-function mutants from patients interacted strongly with STEEP, leading to increased ER PtdIns(3)P levels and membrane curvature. Thus, STEEP enables STING signaling by promoting ER exit.

KW - CYCLIC GMP-AMP

KW - INNATE IMMUNITY

KW - DNA VIRUSES

KW - ADAPTER

KW - TRANSLOCATION

KW - PHOSPHORYLATION

KW - 2ND-MESSENGER

KW - AUTOPHAGY

KW - SYNTHASE

U2 - 10.1038/s41590-020-0730-5

DO - 10.1038/s41590-020-0730-5

M3 - Journal article

C2 - 32690950

VL - 21

SP - 868-+

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 8

ER -

ID: 246784787