Author: Saul, Vera Vivian; Seibert, Markus; Krüger, Marcus; Jeratsch, Sylvia; Kracht, Michael; Schmitz, Michael Lienhard
Title: ULK1/2 Restricts the Formation of Inducible SINT-Speckles, Membraneless Organelles Controlling the Threshold of TBK1 Activation Document date: 2019_8_6
ID: 5xk3z4ck_4
Snippet: Here we have studied the intracellular distribution of SINTBAD and found its stress-regulated incorporation into cytosolic speckles not corresponding to the known MLO members that were tested. Determination of the SINTBAD interactome allowed the identification of proteins contained in constitutive and inducible SINT-speckles or as regulators of this dynamic process. The formation of inducible SINT-speckles is inhibited by the constitutive chapero.....
Document: Here we have studied the intracellular distribution of SINTBAD and found its stress-regulated incorporation into cytosolic speckles not corresponding to the known MLO members that were tested. Determination of the SINTBAD interactome allowed the identification of proteins contained in constitutive and inducible SINT-speckles or as regulators of this dynamic process. The formation of inducible SINT-speckles is inhibited by the constitutive chaperone activity of heat shock proteins (HSPs) and ULK1 signaling, whereas KAT2A (also referred to as GCN5) promotes SINT-speckle formation. The SINT-speckle components AZI2 and SINTBAD determine the threshold of TBK1 activation, which partially occurs within SINT-speckles. Knockdown of ULK1/2 was sufficient to trigger SINT-speckle formation, but interfered with focal TBK1 activation in a pathway-specific fashion.
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