Microspherule protein 2 associates with ASK1 and acts as a negative regulator of stress-induced ASK1 activation

• Published in: FEBS letters Vol. 586; no. 12; pp. 1678 - 1686
• Main Authors: Xu, Mafei, Zhang, Fang, Da, Liang, Li, Tsaiping, Zhao, Mujun
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 12.06.2012
• Subjects: Apoptosis; apoptosis signal-regulating kinase 1; ASK1; c-Jun NH2-terminal kinase; Daxx; death domain-associated protein; Enzyme Activation; Enzyme Induction; Feedback, Physiological; Gene Knockdown Techniques; H2O2; HEK293 Cells; HeLa Cells; Humans; Hydrogen peroxide; Hydrogen Peroxide - antagonists & inhibitors; Hydrogen Peroxide - metabolism; JNK; MAP Kinase Kinase Kinase 5 - chemistry; MAP Kinase Kinase Kinase 5 - metabolism; MCRS2; microspherule protein 2; microspherule protein 58 kDa; MSP58; Nuclear Proteins - chemistry; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oxidants - antagonists & inhibitors; Oxidants - metabolism; Oxidative Stress; phosphatase and tensin homologue; Phosphorylation; Protein Binding; Protein degradation; Protein Interaction Domains and Motifs; Protein Transport; Proteolysis; PTEN; RNA-Binding Proteins - chemistry; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; short hairpin RNA; shRNA; Protein degradation; Hydrogen peroxide; shRNA; ASK1; JNK; MCRS2; PTEN; H2O2; Daxx; MSP58; Apoptosis
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2012.04.051

► MCRS2 interacts with ASK1 directly. ► ASK1 sequesters MCRS2 in the cytoplasm. ► Overexpression of MCRS2 inhibits H2O2-induced ASK1 phosphorylation. ► Knockdown of MCRS2 accelerates the activation of ASK1 signal pathway. ► H2O2 treatment results in the degradation of MCRS2. 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 (H2O2)-induced ASK1 activation. Knockdown of MCRS2 expression accelerated p38 and JNK phosphorylation and promoted apoptosis in response to H2O2. Finally, H2O2 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. Structured summary of protein interactions MCRS2physically interacts with ASK1 by anti tag coimmunoprecipitation (View interaction) MCRS2physically interacts with ASK1 by anti bait coimmunoprecipitation (View interaction) MCRS2physically interacts with Daxx by anti tag coimmunoprecipitation (View interaction) ASK1 and MCRS2colocalize by fluorescence microscopy (View interaction)