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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.



Abstract

During beta -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-1 alpha. 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-1 alpha ...

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