Central Role of ULK1 in Type I Interferon Signaling

Diana Saleiro; Swarna Mehrotra; Barbara Kroczynska; Elspeth M. Beauchamp; Pawel Lisowski; Beata Majchrzak-Kita; Tushar D. Bhagat; Brady L. Stein; Brandon McMahon; Jessica K. Altman; Ewa M. Kosciuczuk; Darren P. Baker; Chunfa Jie; Nadereh Jafari; Craig B. Thompson; Ross L. Levine; Eleanor N. Fish; Amit K. Verma; Leonidas C. Platanias

doi:10.1016/j.celrep.2015.03.056

Central Role of ULK1 in Type I Interferon Signaling

Diana Saleiro, Swarna Mehrotra, Barbara Kroczynska, Elspeth M. Beauchamp, Pawel Lisowski, Beata Majchrzak-Kita, Tushar D. Bhagat, Brady L. Stein, Brandon McMahon, Jessica K. Altman, Ewa M. Kosciuczuk, Darren P. Baker, Chunfa Jie, Nadereh Jafari, Craig B. Thompson, Ross L. Levine, Eleanor N. Fish, Amit K. Verma, Leonidas C. Platanias

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Abstract

We provide evidence that the Unc-51-like kinase 1 (ULK1) is activated during engagement of the type I interferon (IFN) receptor (IFNR). Our studies demonstrate that the function of ULK1 is required for gene transcription mediated via IFN-stimulated response elements (ISRE) and IFNγ activation site (GAS) elements and controls expression of key IFN-stimulated genes (ISGs). We identify ULK1 as an upstream regulator of p38α mitogen-activated protein kinase (MAPK) and establish that the regulatory effects ofULK1 on ISG expression are mediated possibly by engagement of the p38 MAPK pathway. Importantly, we demonstrate that ULK1 is essential for antiproliferative responses and type I IFN-induced antineoplastic effects against malignant erythroid precursors from patients with myeloproliferative neoplasms. Together, these data reveal a role for ULK1 as a key mediator of type I IFNR-generated signals that control gene transcription and induction ofantineoplastic responses.

Original language	English (US)
Pages (from-to)	605-617
Number of pages	13
Journal	Cell Reports
Volume	11
Issue number	4
DOIs	https://doi.org/10.1016/j.celrep.2015.03.056
State	Published - Apr 28 2015

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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Saleiro, D., Mehrotra, S., Kroczynska, B., Beauchamp, E. M., Lisowski, P., Majchrzak-Kita, B., Bhagat, T. D., Stein, B. L., McMahon, B., Altman, J. K., Kosciuczuk, E. M., Baker, D. P., Jie, C., Jafari, N., Thompson, C. B., Levine, R. L., Fish, E. N., Verma, A. K., & Platanias, L. C. (2015). Central Role of ULK1 in Type I Interferon Signaling. Cell Reports, 11(4), 605-617. https://doi.org/10.1016/j.celrep.2015.03.056

Saleiro, D, Mehrotra, S, Kroczynska, B, Beauchamp, EM, Lisowski, P, Majchrzak-Kita, B, Bhagat, TD, Stein, BL, McMahon, B, Altman, JK, Kosciuczuk, EM, Baker, DP, Jie, C, Jafari, N, Thompson, CB, Levine, RL, Fish, EN, Verma, AK & Platanias, LC 2015, 'Central Role of ULK1 in Type I Interferon Signaling', Cell Reports, vol. 11, no. 4, pp. 605-617. https://doi.org/10.1016/j.celrep.2015.03.056

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title = "Central Role of ULK1 in Type I Interferon Signaling",

abstract = "We provide evidence that the Unc-51-like kinase 1 (ULK1) is activated during engagement of the type I interferon (IFN) receptor (IFNR). Our studies demonstrate that the function of ULK1 is required for gene transcription mediated via IFN-stimulated response elements (ISRE) and IFNγ activation site (GAS) elements and controls expression of key IFN-stimulated genes (ISGs). We identify ULK1 as an upstream regulator of p38α mitogen-activated protein kinase (MAPK) and establish that the regulatory effects ofULK1 on ISG expression are mediated possibly by engagement of the p38 MAPK pathway. Importantly, we demonstrate that ULK1 is essential for antiproliferative responses and type I IFN-induced antineoplastic effects against malignant erythroid precursors from patients with myeloproliferative neoplasms. Together, these data reveal a role for ULK1 as a key mediator of type I IFNR-generated signals that control gene transcription and induction ofantineoplastic responses.",

author = "Diana Saleiro and Swarna Mehrotra and Barbara Kroczynska and Beauchamp, {Elspeth M.} and Pawel Lisowski and Beata Majchrzak-Kita and Bhagat, {Tushar D.} and Stein, {Brady L.} and Brandon McMahon and Altman, {Jessica K.} and Kosciuczuk, {Ewa M.} and Baker, {Darren P.} and Chunfa Jie and Nadereh Jafari and Thompson, {Craig B.} and Levine, {Ross L.} and Fish, {Eleanor N.} and Verma, {Amit K.} and Platanias, {Leonidas C.}",

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doi = "10.1016/j.celrep.2015.03.056",

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T1 - Central Role of ULK1 in Type I Interferon Signaling

AU - Saleiro, Diana

AU - Mehrotra, Swarna

AU - Kroczynska, Barbara

AU - Beauchamp, Elspeth M.

AU - Lisowski, Pawel

AU - Majchrzak-Kita, Beata

AU - Bhagat, Tushar D.

AU - Stein, Brady L.

AU - McMahon, Brandon

AU - Altman, Jessica K.

AU - Kosciuczuk, Ewa M.

AU - Baker, Darren P.

AU - Jie, Chunfa

AU - Jafari, Nadereh

AU - Thompson, Craig B.

AU - Levine, Ross L.

AU - Fish, Eleanor N.

AU - Verma, Amit K.

AU - Platanias, Leonidas C.

PY - 2015/4/28

Y1 - 2015/4/28

N2 - We provide evidence that the Unc-51-like kinase 1 (ULK1) is activated during engagement of the type I interferon (IFN) receptor (IFNR). Our studies demonstrate that the function of ULK1 is required for gene transcription mediated via IFN-stimulated response elements (ISRE) and IFNγ activation site (GAS) elements and controls expression of key IFN-stimulated genes (ISGs). We identify ULK1 as an upstream regulator of p38α mitogen-activated protein kinase (MAPK) and establish that the regulatory effects ofULK1 on ISG expression are mediated possibly by engagement of the p38 MAPK pathway. Importantly, we demonstrate that ULK1 is essential for antiproliferative responses and type I IFN-induced antineoplastic effects against malignant erythroid precursors from patients with myeloproliferative neoplasms. Together, these data reveal a role for ULK1 as a key mediator of type I IFNR-generated signals that control gene transcription and induction ofantineoplastic responses.

AB - We provide evidence that the Unc-51-like kinase 1 (ULK1) is activated during engagement of the type I interferon (IFN) receptor (IFNR). Our studies demonstrate that the function of ULK1 is required for gene transcription mediated via IFN-stimulated response elements (ISRE) and IFNγ activation site (GAS) elements and controls expression of key IFN-stimulated genes (ISGs). We identify ULK1 as an upstream regulator of p38α mitogen-activated protein kinase (MAPK) and establish that the regulatory effects ofULK1 on ISG expression are mediated possibly by engagement of the p38 MAPK pathway. Importantly, we demonstrate that ULK1 is essential for antiproliferative responses and type I IFN-induced antineoplastic effects against malignant erythroid precursors from patients with myeloproliferative neoplasms. Together, these data reveal a role for ULK1 as a key mediator of type I IFNR-generated signals that control gene transcription and induction ofantineoplastic responses.

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Central Role of ULK1 in Type I Interferon Signaling

Abstract

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