title: Jab1 interacts with brain-specific kinase 2 (BRSK2) and promotes its degradation in the ubiquitin-proteasome pathway.
abstract: Brain-specific kinase 2 (BRSK2) was classified as an AMP-activated protein kinase (AMPK)-related kinase and one of the substrates of LKB1. Studies on homologs of BRSK2 in mice, SADA and SADB, implied that it might be involved in the regulation of cell polarity and cell cycle. However, physiological functions and molecular regulatory mechanisms of BRSK2 are incompletely understood. In this study, we isolated a novel BRSK2-interacting protein, c-Jun activation domain-binding protein-1 (Jab1), which was reported to mediate degradation of multiple proteins and positively regulate cell cycle progression. GST pull-down and immunoprecipitation assays revealed the direct interaction between BRSK2 and Jab1 in vitro and in vivo, respectively. The co-localization between Jab1 and BRSK2 in the perinuclear region was observed. Intriguingly, Jab1 promoted the ubiquitination and proteasome-dependent degradation of BRSK2. Silencing of endogenous Jab1 increased the cellular BRSK2 protein level. Consistent with this, BRSK2-mediated cell cycle arrest at the G2/M phase in mammalian cells was reversed by exogenous Jab1. Taken together, our findings provide a novel regulatory mechanism of BRSK2 through direct interaction with Jab1.
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Bo
authors.initials: B
authors.lastname: Wan
authors.forename: Ruwei
authors.initials: R
authors.lastname: Li
authors.forename: Xiuting
authors.initials: X
authors.lastname: Gu
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Zhong
authors.forename: Yingli
authors.initials: Y
authors.lastname: Wang
authors.forename: Long
authors.initials: L
authors.lastname: Yu
mesh_terms: D000818:Animals; D000075686:COP9 Signalosome Complex; D059565:G2 Phase Cell Cycle Checkpoints; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D059566:M Phase Cell Cycle Checkpoints; D051379:Mice; D010447:Peptide Hydrolases / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D059748:Proteolysis; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D025801:Ubiquitin; C507732:Brsk2 protein, human; D017346:Protein Serine-Threonine Kinases; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex; D046988:Proteasome Endopeptidase Complex