Telomere dysfunction activates YAP1 to drive tissue inflammation

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Telomere dysfunction activates YAP1 to drive tissue inflammation. / Chakravarti, Deepavali; Hu, Baoli; Mao, Xizeng; Rashid, Asif; Li, Jiexi; Li, Jun; Liao, Wen ting; Whitley, Elizabeth M.; Dey, Prasenjit; Hou, Pingping; LaBella, Kyle A.; Chang, Andrew; Wang, Guocan; Spring, Denise J.; Deng, Pingna; Zhao, Di; Liang, Xin; Lan, Zhengdao; Lin, Yiyun; Sarkar, Sharmistha; Terranova, Christopher; Deribe, Yonathan Lissanu; Blutt, Sarah E.; Okhuysen, Pablo; Zhang, Jianhua; Vilar, Eduardo; Nielsen, Ole Haagen; Dupont, Andrew; Younes, Mamoun; Patel, Kalyani R.; Shroyer, Noah F.; Rai, Kunal; Estes, Mary K.; Wang, Y. Alan; Bertuch, Alison A.; DePinho, Ronald A.

I: Nature Communications, Bind 11, 4766, 2020.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Chakravarti, D, Hu, B, Mao, X, Rashid, A, Li, J, Li, J, Liao, WT, Whitley, EM, Dey, P, Hou, P, LaBella, KA, Chang, A, Wang, G, Spring, DJ, Deng, P, Zhao, D, Liang, X, Lan, Z, Lin, Y, Sarkar, S, Terranova, C, Deribe, YL, Blutt, SE, Okhuysen, P, Zhang, J, Vilar, E, Nielsen, OH, Dupont, A, Younes, M, Patel, KR, Shroyer, NF, Rai, K, Estes, MK, Wang, YA, Bertuch, AA & DePinho, RA 2020, 'Telomere dysfunction activates YAP1 to drive tissue inflammation', Nature Communications, bind 11, 4766. https://doi.org/10.1038/s41467-020-18420-w

APA

Chakravarti, D., Hu, B., Mao, X., Rashid, A., Li, J., Li, J., Liao, W. T., Whitley, E. M., Dey, P., Hou, P., LaBella, K. A., Chang, A., Wang, G., Spring, D. J., Deng, P., Zhao, D., Liang, X., Lan, Z., Lin, Y., ... DePinho, R. A. (2020). Telomere dysfunction activates YAP1 to drive tissue inflammation. Nature Communications, 11, [4766]. https://doi.org/10.1038/s41467-020-18420-w

Vancouver

Chakravarti D, Hu B, Mao X, Rashid A, Li J, Li J o.a. Telomere dysfunction activates YAP1 to drive tissue inflammation. Nature Communications. 2020;11. 4766. https://doi.org/10.1038/s41467-020-18420-w

Author

Chakravarti, Deepavali ; Hu, Baoli ; Mao, Xizeng ; Rashid, Asif ; Li, Jiexi ; Li, Jun ; Liao, Wen ting ; Whitley, Elizabeth M. ; Dey, Prasenjit ; Hou, Pingping ; LaBella, Kyle A. ; Chang, Andrew ; Wang, Guocan ; Spring, Denise J. ; Deng, Pingna ; Zhao, Di ; Liang, Xin ; Lan, Zhengdao ; Lin, Yiyun ; Sarkar, Sharmistha ; Terranova, Christopher ; Deribe, Yonathan Lissanu ; Blutt, Sarah E. ; Okhuysen, Pablo ; Zhang, Jianhua ; Vilar, Eduardo ; Nielsen, Ole Haagen ; Dupont, Andrew ; Younes, Mamoun ; Patel, Kalyani R. ; Shroyer, Noah F. ; Rai, Kunal ; Estes, Mary K. ; Wang, Y. Alan ; Bertuch, Alison A. ; DePinho, Ronald A. / Telomere dysfunction activates YAP1 to drive tissue inflammation. I: Nature Communications. 2020 ; Bind 11.

Bibtex

@article{693adc03fa4b42ac98d56440a94416c9,
title = "Telomere dysfunction activates YAP1 to drive tissue inflammation",
abstract = "Germline telomere maintenance defects are associated with an increased incidence of inflammatory diseases in humans, yet whether and how telomere dysfunction causes inflammation are not known. Here, we show that telomere dysfunction drives pATM/c-ABL-mediated activation of the YAP1 transcription factor, up-regulating the major pro-inflammatory factor, pro-IL-18. The colonic microbiome stimulates cytosolic receptors activating caspase-1 which cleaves pro-IL-18 into mature IL-18, leading to recruitment of interferon (IFN)-γ-secreting T cells and intestinal inflammation. Correspondingly, patients with germline telomere maintenance defects exhibit DNA damage (γH2AX) signaling together with elevated YAP1 and IL-18 expression. In mice with telomere dysfunction, telomerase reactivation in the intestinal epithelium or pharmacological inhibition of ATM, YAP1, or caspase-1 as well as antibiotic treatment, dramatically reduces IL-18 and intestinal inflammation. Thus, telomere dysfunction-induced activation of the ATM-YAP1-pro-IL-18 pathway in epithelium is a key instigator of tissue inflammation.",
author = "Deepavali Chakravarti and Baoli Hu and Xizeng Mao and Asif Rashid and Jiexi Li and Jun Li and Liao, {Wen ting} and Whitley, {Elizabeth M.} and Prasenjit Dey and Pingping Hou and LaBella, {Kyle A.} and Andrew Chang and Guocan Wang and Spring, {Denise J.} and Pingna Deng and Di Zhao and Xin Liang and Zhengdao Lan and Yiyun Lin and Sharmistha Sarkar and Christopher Terranova and Deribe, {Yonathan Lissanu} and Blutt, {Sarah E.} and Pablo Okhuysen and Jianhua Zhang and Eduardo Vilar and Nielsen, {Ole Haagen} and Andrew Dupont and Mamoun Younes and Patel, {Kalyani R.} and Shroyer, {Noah F.} and Kunal Rai and Estes, {Mary K.} and Wang, {Y. Alan} and Bertuch, {Alison A.} and DePinho, {Ronald A.}",
year = "2020",
doi = "10.1038/s41467-020-18420-w",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Telomere dysfunction activates YAP1 to drive tissue inflammation

AU - Chakravarti, Deepavali

AU - Hu, Baoli

AU - Mao, Xizeng

AU - Rashid, Asif

AU - Li, Jiexi

AU - Li, Jun

AU - Liao, Wen ting

AU - Whitley, Elizabeth M.

AU - Dey, Prasenjit

AU - Hou, Pingping

AU - LaBella, Kyle A.

AU - Chang, Andrew

AU - Wang, Guocan

AU - Spring, Denise J.

AU - Deng, Pingna

AU - Zhao, Di

AU - Liang, Xin

AU - Lan, Zhengdao

AU - Lin, Yiyun

AU - Sarkar, Sharmistha

AU - Terranova, Christopher

AU - Deribe, Yonathan Lissanu

AU - Blutt, Sarah E.

AU - Okhuysen, Pablo

AU - Zhang, Jianhua

AU - Vilar, Eduardo

AU - Nielsen, Ole Haagen

AU - Dupont, Andrew

AU - Younes, Mamoun

AU - Patel, Kalyani R.

AU - Shroyer, Noah F.

AU - Rai, Kunal

AU - Estes, Mary K.

AU - Wang, Y. Alan

AU - Bertuch, Alison A.

AU - DePinho, Ronald A.

PY - 2020

Y1 - 2020

N2 - Germline telomere maintenance defects are associated with an increased incidence of inflammatory diseases in humans, yet whether and how telomere dysfunction causes inflammation are not known. Here, we show that telomere dysfunction drives pATM/c-ABL-mediated activation of the YAP1 transcription factor, up-regulating the major pro-inflammatory factor, pro-IL-18. The colonic microbiome stimulates cytosolic receptors activating caspase-1 which cleaves pro-IL-18 into mature IL-18, leading to recruitment of interferon (IFN)-γ-secreting T cells and intestinal inflammation. Correspondingly, patients with germline telomere maintenance defects exhibit DNA damage (γH2AX) signaling together with elevated YAP1 and IL-18 expression. In mice with telomere dysfunction, telomerase reactivation in the intestinal epithelium or pharmacological inhibition of ATM, YAP1, or caspase-1 as well as antibiotic treatment, dramatically reduces IL-18 and intestinal inflammation. Thus, telomere dysfunction-induced activation of the ATM-YAP1-pro-IL-18 pathway in epithelium is a key instigator of tissue inflammation.

AB - Germline telomere maintenance defects are associated with an increased incidence of inflammatory diseases in humans, yet whether and how telomere dysfunction causes inflammation are not known. Here, we show that telomere dysfunction drives pATM/c-ABL-mediated activation of the YAP1 transcription factor, up-regulating the major pro-inflammatory factor, pro-IL-18. The colonic microbiome stimulates cytosolic receptors activating caspase-1 which cleaves pro-IL-18 into mature IL-18, leading to recruitment of interferon (IFN)-γ-secreting T cells and intestinal inflammation. Correspondingly, patients with germline telomere maintenance defects exhibit DNA damage (γH2AX) signaling together with elevated YAP1 and IL-18 expression. In mice with telomere dysfunction, telomerase reactivation in the intestinal epithelium or pharmacological inhibition of ATM, YAP1, or caspase-1 as well as antibiotic treatment, dramatically reduces IL-18 and intestinal inflammation. Thus, telomere dysfunction-induced activation of the ATM-YAP1-pro-IL-18 pathway in epithelium is a key instigator of tissue inflammation.

U2 - 10.1038/s41467-020-18420-w

DO - 10.1038/s41467-020-18420-w

M3 - Journal article

C2 - 32958778

AN - SCOPUS:85091305538

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 4766

ER -

ID: 249156732