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. P62^Δ69-251 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 p62^Δ69-251 mice, global p62^-/- and Ucp1-Cre p62^flx/flx mice. BAT dysfunction resulting from p62 deficiency is manifest after birth and obesity s

SUBMITTER: Fischer K 

PROVIDER: S-EPMC7211001 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature