Universität zu Köln

Saul, Vera Vivian, Seibert, Markus ORCID: 0000-0001-5708-4856, Krueger, Marcus ORCID: 0000-0003-2008-4582, Jeratsch, Sylvia, Kracht, Michael and Schmitz, Michael Lienhard (2019). ULK1/2 Restricts the Formation of Inducible SINT-Speckles, Membraneless Organelles Controlling the Threshold of TBK1 Activation. iScience, 19. S. 527 - 565. CAMBRIDGE: CELL PRESS. ISSN 2589-0042

Full text not available from this repository.

Abstract

Membraneless organelles (MLOs) are liquid-like subcellular compartments providing spatiotemporal control to biological processes. This study reveals that cellular stress leads to the incorporation of the adaptor protein SINTBAD (TBKBP1) into membraneless, cytosolic speckles. Determination of the interactome identified >100 proteins forming constitutive and stress-inducible members of an MLO that we termed SINT-speckles. SINT-speckles partially colocalize with activated TBK1, and deletion of SINTBAD and the SINT-speckle component AZ12 leads to impaired TBK1 phosphorylation. Dynamic formation of SINT-speckles is positively controlled by the acetyltransferase KAT2A (GCN5) and antagonized by heat shock protein-mediated chaperone activity. SINT-speckle formation is also inhibited by the autophagy-initiating kinases ULK1/2, and knockdown of these kinases prevented focal TBK1 phosphorylation in a pathway-specific manner. The phlebovirus-encoded non-structural protein S enhances ULK1-mediated TBK1 phosphorylation and shows a stress-induced translocation to SINT-speckles, raising the possibility that viruses can also target this signaling hub to manipulate host cell functions.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Saul, Vera Vivian UNSPECIFIED UNSPECIFIED UNSPECIFIED Seibert, Markus UNSPECIFIED orcid.org/0000-0001-5708-4856 UNSPECIFIED Krueger, Marcus UNSPECIFIED orcid.org/0000-0003-2008-4582 UNSPECIFIED Jeratsch, Sylvia UNSPECIFIED UNSPECIFIED UNSPECIFIED Kracht, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmitz, Michael Lienhard UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-133595
DOI:	10.1016/j.isci.2019.08.001
Journal or Publication Title:	iScience
Volume:	19
Page Range:	S. 527 - 565
Date:	2019
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	2589-0042
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NF-KAPPA-B; PHASE-SEPARATION; STRESS GRANULES; METABOLIC-REGULATION; LIPID-METABOLISM; PROTEIN; AUTOPHAGY; KINASE; CHAPERONE; INNATE Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13359