The F-box Protein KIB1 Mediates Brassinosteroid-Induced Inactivation and Degradation of GSK3-like Kinases in Arabidopsis

• Published in: Molecular cell Vol. 66; no. 5; pp. 648 - 657.e4
• Main Authors: Zhu, Jia-Ying, Li, Yuyao, Cao, Dong-Mei, Yang, Hongjuan, Oh, Eunkyoo, Bi, Yang, Zhu, Shengwei, Wang, Zhi-Yong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2017
• Subjects: Arabidopsis; Arabidopsis - drug effects; Arabidopsis - enzymology; Arabidopsis - genetics; Arabidopsis Proteins - genetics; Arabidopsis Proteins - metabolism; BIN2; Binding Sites; brassinosteroid; Brassinosteroids - pharmacology; Catalytic Domain; E3 ubiquitin ligase; Enzyme Activation; Enzyme Stability; F-box protein; F-Box Proteins - genetics; F-Box Proteins - metabolism; Genotype; Glycogen Synthase Kinase 3 - genetics; Glycogen Synthase Kinase 3 - metabolism; GSK3; GSK3 degradation; Mutation; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Phenotype; Plant Growth Regulators - pharmacology; Plants, Genetically Modified - drug effects; Plants, Genetically Modified - enzymology; Plants, Genetically Modified - genetics; proteasome; Proteasome Endopeptidase Complex - metabolism; Protein Binding; Protein Kinases - genetics; Protein Kinases - metabolism; Proteolysis; Signal Transduction - drug effects; steroid hormone; Steroids, Heterocyclic - pharmacology; Substrate Specificity; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; Ubiquitination; proteasome; steroid hormone; BIN2; GSK3; Arabidopsis; ubiquitination; F-box protein; GSK3 degradation; E3 ubiquitin ligase; brassinosteroid
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2017.05.012

The glycogen synthase kinase-3 (GSK3) family kinases are central cellular regulators highly conserved in all eukaryotes. In Arabidopsis, the GSK3-like kinase BIN2 phosphorylates a range of proteins to control broad developmental processes, and BIN2 is degraded through unknown mechanism upon receptor kinase-mediated brassinosteroid (BR) signaling. Here we identify KIB1 as an F-box E3 ubiquitin ligase that promotes the degradation of BIN2 while blocking its substrate access. Loss-of-function mutations of KIB1 and its homologs abolished BR-induced BIN2 degradation and caused severe BR-insensitive phenotypes. KIB1 directly interacted with BIN2 in a BR-dependent manner and promoted BIN2 ubiquitination in vitro. Expression of an F-box-truncated KIB1 caused BIN2 accumulation but dephosphorylation of its substrate BZR1 and activation of BR responses because KIB1 blocked BIN2 binding to BZR1. Our study demonstrates that KIB1 plays an essential role in BR signaling by inhibiting BIN2 through dual mechanisms of blocking substrate access and promoting degradation. [Display omitted] •KIB1 is an essential positive regulator in brassinosteroid signaling•KIB1 mediates BR-induced ubiquitination and degradation of GSK3 kinase BIN2•KIB1 binding to BIN2 prevents BIN2-substrate interaction and promotes BIN2 degradation Zhu et al. identify KIB1 as an F-box E3 ubiquitin ligase required for brassinosteroid signal transduction and further reveal a dual mechanism of KIB1-mediating GSK3 inactivation: blocking substrate access by the same binding event that leads subsequently to its ubiquitination and proteasomal degradation.