@article {36606,
	title = {An intrinsic temporal order of c-JUN N-terminal phosphorylation regulates its activity by orchestrating co-factor recruitment},
	journal = {Nat Commun},
	volume = {13},
	number = {1},
	year = {2022},
	note = {Waudby, Christopher AAlvarez-Teijeiro, SaulJosue Ruiz, ESuppinger, SimonPinotsis, NikosBrown, Paul RBehrens, AxelChristodoulou, JohnMylona, Anastasiaeng204770/Z/16/Z/WT_/Wellcome Trust/United KingdomBB/T002603/1/BB_/Biotechnology and Biological Sciences Research Council/United KingdomResearch Support, Non-U.S. Gov{\textquoteright}tEnglandNat Commun. 2022 Oct 17;13(1):6133. doi: 10.1038/s41467-022-33866-w.},
	month = {Oct 17},
	pages = {6133},
	edition = {2022/10/18},
	abstract = {Protein phosphorylation is a major regulatory mechanism of cellular signalling. The c-JUN proto-oncoprotein is phosphorylated at four residues within its transactivation domain (TAD) by the JNK family kinases, but the functional significance of c-JUN multisite phosphorylation has remained elusive. Here we show that c-JUN phosphorylation by JNK exhibits defined temporal kinetics, with serine63 and serine73 being phosphorylated more rapidly than threonine91 and threonine93. We identify the positioning of the phosphorylation sites relative to the kinase docking motif, and their primary sequence, as the main factors controlling phosphorylation kinetics. Functional analysis reveals three c-JUN phosphorylation states: unphosphorylated c-JUN recruits the MBD3 repressor, serine63/73 doubly-phosphorylated c-JUN binds to the TCF4 co-activator, whereas the fully phosphorylated form disfavours TCF4 binding attenuating JNK signalling. Thus, c-JUN phosphorylation encodes multiple functional states that drive a complex signalling response from a single JNK input.},
	keywords = {*JNK Mitogen-Activated Protein Kinases/metabolism, *Proto-Oncogene Proteins c-jun/metabolism, MAP Kinase Kinase 4/metabolism, MAP Kinase Signaling System, Phosphorylation, signal transduction},
	isbn = {2041-1723 (Electronic)2041-1723 (Linking)},
	author = {Waudby, C. A. and Alvarez-Teijeiro, S. and Josue Ruiz, E. and Suppinger, S. and Pinotsis, N. and Brown, P. R. and Behrens, A. and Christodoulou, J and Mylona, A}
}
