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The scaffold protei...
The scaffold protein p62 regulates adaptive thermogenesis through ATF2 nuclear target activation
- Article/chapterEnglish2020
Publisher, publication year, extent ...
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2020-05-08
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Springer Science and Business Media LLC,2020
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:su-183009
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https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-183009URI
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https://doi.org/10.1038/s41467-020-16230-8DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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 promoter. P62(Delta 69-251) mice show reduced expression of Ucp1 and Pgc-1 alpha with impaired ATF2 genomic binding. Modulation of Ucp1 and Pgc-1 alpha expression through p62 regulation of ATF2 signaling is demonstrated in vitro and in vivo in p62(Delta 69-251) mice, global p62(-/-) and Ucp1-Cre p62(flx/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. Beta-adrenergic stimulation of brown adipose tissue leads to thermogenesis via the activating transcription factor 2 (ATF2) mediated expression of the thermogenic genes Ucp1 and Pgc-1 alpha. Here, the authors show that the scaffold protein p62 regulates brown adipose tissue function through modifying ATF2 genomic binding and subsequent Ucp1 and Pgc-1 alpha induction.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Fenzl, Anna
(author)
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Liu, Dianxin
(author)
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Dyar, Kenneth A.
(author)
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Kleinert, Maximilian
(author)
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Brielmeier, Markus
(author)
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Clemmensen, Christoffer
(author)
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Fedl, Anna
(author)
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Finan, Brian
(author)
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Gessner, Andre
(author)
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Jastroch, MartinStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,Helmholtz Diabetes Center (HDC), Germany; German National Diabetes Center (DZD), Germany(Swepub:su)maja7434
(author)
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Huang, Jianfeng
(author)
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Keipert, SusanneStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,Helmholtz Diabetes Center (HDC), Germany; German National Diabetes Center (DZD), Germany(Swepub:su)suke3968
(author)
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Klingenspor, Martin
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Brüning, Jens C.
(author)
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Kneilling, Manfred
(author)
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Maier, Florian C.
(author)
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Othman, Ahmed E.
(author)
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Pichler, Bernd J.
(author)
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Pramme-Steinwachs, Ines
(author)
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Sachs, Stephan
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Scheideler, Angelika
(author)
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Thaiss, Wolfgang M.
(author)
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Uhlenhaut, Henriette
(author)
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Ussar, Siegfried
(author)
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Woods, Stephen C.
(author)
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Zorn, Julia
(author)
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Stemmer, Kerstin
(author)
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Collins, Sheila
(author)
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Diaz-Meco, Maria
(author)
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Moscat, Jorge
(author)
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Tschöp, Matthias H.
(author)
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Müller, Timo D.
(author)
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Stockholms universitetInstitutionen för molekylär biovetenskap, Wenner-Grens institut
(creator_code:org_t)
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In:Nature Communications: Springer Science and Business Media LLC11:12041-1723
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- By the author/editor
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Fischer, Katrin
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Fenzl, Anna
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Liu, Dianxin
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Dyar, Kenneth A.
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Kleinert, Maximi ...
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Brielmeier, Mark ...
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show more...
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Clemmensen, Chri ...
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Fedl, Anna
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Finan, Brian
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Gessner, Andre
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Jastroch, Martin
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Huang, Jianfeng
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Keipert, Susanne
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Klingenspor, Mar ...
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Brüning, Jens C.
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Kneilling, Manfr ...
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Maier, Florian C ...
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Othman, Ahmed E.
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Pichler, Bernd J ...
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Pramme-Steinwach ...
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Sachs, Stephan
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Scheideler, Ange ...
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Thaiss, Wolfgang ...
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Uhlenhaut, Henri ...
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Ussar, Siegfried
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Woods, Stephen C ...
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Zorn, Julia
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Stemmer, Kerstin
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Collins, Sheila
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Diaz-Meco, Maria
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Moscat, Jorge
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Tschöp, Matthias ...
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Müller, Timo D.
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
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Nature Communica ...
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Stockholm University