The scaffold protein p62 regulates adaptive thermogenesis through ATF2 nuclear target activation

Research output: Contribution to journal › Journal article › Research › peer-review

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The scaffold protein p62 regulates adaptive thermogenesis through ATF2 nuclear target activation. / Fischer, Katrin; Fenzl, Anna; Liu, Dianxin; Dyar, Kenneth A; Kleinert, Maximilian; Brielmeier, Markus; Clemmensen, Christoffer; Fedl, Anna; Finan, Brian; Gessner, Andre; Jastroch, Martin; Huang, Jianfeng; Keipert, Susanne; Klingenspor, Martin; Brüning, Jens C; Kneilling, Manfred; Maier, Florian C; Othman, Ahmed E; Pichler, Bernd J; Pramme-Steinwachs, Ines; Sachs, Stephan; Scheideler, Angelika; Thaiss, Wolfgang M; Uhlenhaut, Henriette; Ussar, Siegfried; Woods, Stephen C; Zorn, Julia; Stemmer, Kerstin; Collins, Sheila; Diaz-Meco, Maria; Moscat, Jorge; Tschöp, Matthias H; Müller, Timo D.

In: Nature Communications, Vol. 11, No. 1, 2306, 2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Fischer, K, Fenzl, A, Liu, D, Dyar, KA, Kleinert, M, Brielmeier, M, Clemmensen, C, Fedl, A, Finan, B, Gessner, A, Jastroch, M, Huang, J, Keipert, S, Klingenspor, M, Brüning, JC, Kneilling, M, Maier, FC, Othman, AE, Pichler, BJ, Pramme-Steinwachs, I, Sachs, S, Scheideler, A, Thaiss, WM, Uhlenhaut, H, Ussar, S, Woods, SC, Zorn, J, Stemmer, K, Collins, S, Diaz-Meco, M, Moscat, J, Tschöp, MH & Müller, TD 2020, 'The scaffold protein p62 regulates adaptive thermogenesis through ATF2 nuclear target activation', Nature Communications, vol. 11, no. 1, 2306. https://doi.org/10.1038/s41467-020-16230-8

APA

Fischer, K., Fenzl, A., Liu, D., Dyar, K. A., Kleinert, M., Brielmeier, M., Clemmensen, C., Fedl, A., Finan, B., Gessner, A., Jastroch, M., Huang, J., Keipert, S., Klingenspor, M., Brüning, J. C., Kneilling, M., Maier, F. C., Othman, A. E., Pichler, B. J., ... Müller, T. D. (2020). The scaffold protein p62 regulates adaptive thermogenesis through ATF2 nuclear target activation. Nature Communications, 11(1), [2306]. https://doi.org/10.1038/s41467-020-16230-8

Vancouver

Fischer K, Fenzl A, Liu D, Dyar KA, Kleinert M, Brielmeier M et al. The scaffold protein p62 regulates adaptive thermogenesis through ATF2 nuclear target activation. Nature Communications. 2020;11(1). 2306. https://doi.org/10.1038/s41467-020-16230-8

Author

Fischer, Katrin ; Fenzl, Anna ; Liu, Dianxin ; Dyar, Kenneth A ; Kleinert, Maximilian ; Brielmeier, Markus ; Clemmensen, Christoffer ; Fedl, Anna ; Finan, Brian ; Gessner, Andre ; Jastroch, Martin ; Huang, Jianfeng ; Keipert, Susanne ; Klingenspor, Martin ; Brüning, Jens C ; Kneilling, Manfred ; Maier, Florian C ; Othman, Ahmed E ; Pichler, Bernd J ; Pramme-Steinwachs, Ines ; Sachs, Stephan ; Scheideler, Angelika ; Thaiss, Wolfgang M ; Uhlenhaut, Henriette ; Ussar, Siegfried ; Woods, Stephen C ; Zorn, Julia ; Stemmer, Kerstin ; Collins, Sheila ; Diaz-Meco, Maria ; Moscat, Jorge ; Tschöp, Matthias H ; Müller, Timo D. / The scaffold protein p62 regulates adaptive thermogenesis through ATF2 nuclear target activation. In: Nature Communications. 2020 ; Vol. 11, No. 1.

Bibtex

@article{0c90bba5e3b346a8a93b5a50e4cba4ce,
title = "The scaffold protein p62 regulates adaptive thermogenesis through ATF2 nuclear target activation",
abstract = "During β-adrenergic stimulation of brown adipose tissue (BAT), p38 phosphorylates the activating transcription factor 2 (ATF2) which then translocates to the nucleus to activate the expression of Ucp1 and Pgc-1α. The mechanisms underlying ATF2 target activation are unknown. Here we demonstrate that p62 (Sqstm1) binds to ATF2 to orchestrate activation of the Ucp1 enhancer and Pgc-1α promoter. P62Δ69-251 mice show reduced expression of Ucp1 and Pgc-1α with impaired ATF2 genomic binding. Modulation of Ucp1 and Pgc-1α expression through p62 regulation of ATF2 signaling is demonstrated in vitro and in vivo in p62Δ69-251 mice, global p62-/- and Ucp1-Cre p62flx/flx mice. BAT dysfunction resulting from p62 deficiency is manifest after birth and obesity subsequently develops despite normal food intake, intestinal nutrient absorption and locomotor activity. In summary, our data identify p62 as a master regulator of BAT function in that it controls the Ucp1 pathway through regulation of ATF2 genomic binding.",
author = "Katrin Fischer and Anna Fenzl and Dianxin Liu and Dyar, {Kenneth A} and Maximilian Kleinert and Markus Brielmeier and Christoffer Clemmensen and Anna Fedl and Brian Finan and Andre Gessner and Martin Jastroch and Jianfeng Huang and Susanne Keipert and Martin Klingenspor and Br{\"u}ning, {Jens C} and Manfred Kneilling and Maier, {Florian C} and Othman, {Ahmed E} and Pichler, {Bernd J} and Ines Pramme-Steinwachs and Stephan Sachs and Angelika Scheideler and Thaiss, {Wolfgang M} and Henriette Uhlenhaut and Siegfried Ussar and Woods, {Stephen C} and Julia Zorn and Kerstin Stemmer and Sheila Collins and Maria Diaz-Meco and Jorge Moscat and Tsch{\"o}p, {Matthias H} and M{\"u}ller, {Timo D.}",
note = "CURIS 2020 NEXS 157",
year = "2020",
doi = "10.1038/s41467-020-16230-8",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - The scaffold protein p62 regulates adaptive thermogenesis through ATF2 nuclear target activation

AU - Fischer, Katrin

AU - Fenzl, Anna

AU - Liu, Dianxin

AU - Dyar, Kenneth A

AU - Kleinert, Maximilian

AU - Brielmeier, Markus

AU - Clemmensen, Christoffer

AU - Fedl, Anna

AU - Finan, Brian

AU - Gessner, Andre

AU - Jastroch, Martin

AU - Huang, Jianfeng

AU - Keipert, Susanne

AU - Klingenspor, Martin

AU - Brüning, Jens C

AU - Kneilling, Manfred

AU - Maier, Florian C

AU - Othman, Ahmed E

AU - Pichler, Bernd J

AU - Pramme-Steinwachs, Ines

AU - Sachs, Stephan

AU - Scheideler, Angelika

AU - Thaiss, Wolfgang M

AU - Uhlenhaut, Henriette

AU - Ussar, Siegfried

AU - Woods, Stephen C

AU - Zorn, Julia

AU - Stemmer, Kerstin

AU - Collins, Sheila

AU - Diaz-Meco, Maria

AU - Moscat, Jorge

AU - Tschöp, Matthias H

AU - Müller, Timo D.

N1 - CURIS 2020 NEXS 157

PY - 2020

Y1 - 2020

N2 - During β-adrenergic stimulation of brown adipose tissue (BAT), p38 phosphorylates the activating transcription factor 2 (ATF2) which then translocates to the nucleus to activate the expression of Ucp1 and Pgc-1α. The mechanisms underlying ATF2 target activation are unknown. Here we demonstrate that p62 (Sqstm1) binds to ATF2 to orchestrate activation of the Ucp1 enhancer and Pgc-1α promoter. P62Δ69-251 mice show reduced expression of Ucp1 and Pgc-1α with impaired ATF2 genomic binding. Modulation of Ucp1 and Pgc-1α expression through p62 regulation of ATF2 signaling is demonstrated in vitro and in vivo in p62Δ69-251 mice, global p62-/- and Ucp1-Cre p62flx/flx mice. BAT dysfunction resulting from p62 deficiency is manifest after birth and obesity subsequently develops despite normal food intake, intestinal nutrient absorption and locomotor activity. In summary, our data identify p62 as a master regulator of BAT function in that it controls the Ucp1 pathway through regulation of ATF2 genomic binding.

AB - During β-adrenergic stimulation of brown adipose tissue (BAT), p38 phosphorylates the activating transcription factor 2 (ATF2) which then translocates to the nucleus to activate the expression of Ucp1 and Pgc-1α. The mechanisms underlying ATF2 target activation are unknown. Here we demonstrate that p62 (Sqstm1) binds to ATF2 to orchestrate activation of the Ucp1 enhancer and Pgc-1α promoter. P62Δ69-251 mice show reduced expression of Ucp1 and Pgc-1α with impaired ATF2 genomic binding. Modulation of Ucp1 and Pgc-1α expression through p62 regulation of ATF2 signaling is demonstrated in vitro and in vivo in p62Δ69-251 mice, global p62-/- and Ucp1-Cre p62flx/flx mice. BAT dysfunction resulting from p62 deficiency is manifest after birth and obesity subsequently develops despite normal food intake, intestinal nutrient absorption and locomotor activity. In summary, our data identify p62 as a master regulator of BAT function in that it controls the Ucp1 pathway through regulation of ATF2 genomic binding.

UR - http://www.scopus.com/inward/record.url?scp=85084720487&partnerID=8YFLogxK

U2 - 10.1038/s41467-020-16230-8

DO - 10.1038/s41467-020-16230-8

M3 - Journal article

C2 - 32385399

AN - SCOPUS:85084720487

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 2306

ER -

ID: 241756337