Universität zu Köln

Fang, Jian ORCID: 0000-0003-0096-1146, Ianni, Alessandro ORCID: 0000-0001-7398-589X, Smolka, Christian, Vakhrusheva, Olesya, Nolte, Hendrik, Kruger, Marcus, Wietelmann, Astrid, Simonet, Nicolas G., Adrian-Segarra, Juan M. ORCID: 0000-0002-3712-0554, Vaquero, Alejandro, Braun, Thomas ORCID: 0000-0002-6165-4804 and Bober, Eva (2017). Sirt7 promotes adipogenesis in the mouse by inhibiting autocatalytic activation of Sirt1. Proc. Natl. Acad. Sci. U. S. A., 114 (40). S. E8352 - 10. WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

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Abstract

Sirtuins (Sirt1-Sirt7) are NAD(+)-dependent protein deacetylases/ ADP ribosyltransferases, which play decisive roles in chromatin silencing, cell cycle regulation, cellular differentiation, and metabolism. Different sirtuins control similar cellular processes, suggesting a coordinated mode of action but information about potential cross-regulatory interactions within the sirtuin family is still limited. Here, we demonstrate that Sirt1 requires autodeacetylation to efficiently deacetylate targets such as p53, H3K9, and H4K16. Sirt7 restricts Sirt1 activity by preventing Sirt1 autodeacetylation causing enhanced Sirt1 activity in Sirt7(-/-) mice. Increased Sirt1 activity in Sirt7(-/-) mice blocks PPAR gamma and adipocyte differentiation, thereby diminishing accumulation of white fat. Thus, reduction of Sirt1 activity restores adipogenesis in Sirt7(-/-) adipocytes in vitro and in vivo. We disclosed a principle controlling Sirt1 activity and uncovered an unexpected complexity in the crosstalk between two different sirtuins. We propose that antagonistic interactions between Sirt1 and Sirt7 are pivotal in controlling the signaling network required for maintenance of adipose tissue.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Fang, Jian UNSPECIFIED orcid.org/0000-0003-0096-1146 UNSPECIFIED Ianni, Alessandro UNSPECIFIED orcid.org/0000-0001-7398-589X UNSPECIFIED Smolka, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Vakhrusheva, Olesya UNSPECIFIED UNSPECIFIED UNSPECIFIED Nolte, Hendrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Kruger, Marcus UNSPECIFIED UNSPECIFIED UNSPECIFIED Wietelmann, Astrid UNSPECIFIED UNSPECIFIED UNSPECIFIED Simonet, Nicolas G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Adrian-Segarra, Juan M. UNSPECIFIED orcid.org/0000-0002-3712-0554 UNSPECIFIED Vaquero, Alejandro UNSPECIFIED UNSPECIFIED UNSPECIFIED Braun, Thomas UNSPECIFIED orcid.org/0000-0002-6165-4804 UNSPECIFIED Bober, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-214582
DOI:	10.1073/pnas.1706945114
Journal or Publication Title:	Proc. Natl. Acad. Sci. U. S. A.
Volume:	114
Number:	40
Page Range:	S. E8352 - 10
Date:	2017
Publisher:	NATL ACAD SCIENCES
Place of Publication:	WASHINGTON
ISSN:	0027-8424
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SIRT1-DEPENDENT DEACETYLATION; GENOME INTEGRITY; PPAR-GAMMA; P53; SIRTUINS; CELL; METABOLISM; REGULATOR; DISEASE; STRESS Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21458