title: Microspherule protein 2 associates with ASK1 and acts as a negative regulator of stress-induced ASK1 activation.
abstract: Microspherule protein 2 (MCRS2) has been reported to associate with the cellular function of telomerase inhibition, transcriptional regulation and cellular transformation. Here, we report a novel function of MCRS2 in ASK1 pathway. We found that MCRS2 directly binds to ASK1 in vivo and co-localises with ASK1 in the cytoplasm. Overexpression of MCRS2 inhibited oxidative stress (H(2)O(2))-induced ASK1 activation. Knockdown of MCRS2 expression accelerated p38 and JNK phosphorylation and promoted apoptosis in response to H(2)O(2). Finally, H(2)O(2) treatment induced proteasomal degradation of MCRS2, which was further enhanced by activated ASK1. Our results clearly demonstrate that MCRS2 plays a negative role in stress-induced ASK1 activation.
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China.
authors.forename: Mafei
authors.initials: M
authors.lastname: Xu
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Da
authors.forename: Tsaiping
authors.initials: T
authors.lastname: Li
authors.forename: Mujun
authors.initials: M
authors.lastname: Zhao
mesh_terms: D017209:Apoptosis; D004789:Enzyme Activation; D004790:Enzyme Induction; D025461:Feedback, Physiological; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016877:Oxidants / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D059748:Proteolysis; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C113292:MCRS1 protein, human; D009687:Nuclear Proteins; D016877:Oxidants; D016601:RNA-Binding Proteins; D006861:Hydrogen Peroxide; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human