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

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 MCRS2 physically interacts with ASK1 by anti tag coimmunoprecipitation (View interaction) MCRS2 physically interacts with ASK1 by anti bait coimmunoprecipitation (View interaction) MCRS2 physically interacts with Daxx by anti tag coimmunoprecipitation (View interaction) ASK1 and MCRS2 colocalize by fluorescence microscopy (View interaction) (c) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.