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Evidence of an interaction between Mos and Hsp70: a role of the Mos residue serine 3 in mediating Hsp70 association

Oncogene volume 18, pages 3461–3470 (1999)Cite this article

Abstract

c-Mos is a germ cell-specific MAP kinase kinase kinase (MAPKKK) that plays an essential role during meiotic divisions of oocytes. c-Mos is a key component of an activity, cytostatic factor, required for metaphase II arrest of unfertilized eggs in vertebrates. To understand the regulation of c-Mos, we are investigating c-Mos-interacting proteins. We provide evidence that mouse c-Mos binds to Hsp70, a molecular chaperone. Hsp70 was found to associate with Mos ectopically expressed in COS-1 cells. Mos-Hsp70 complexes could be immunoprecipitated with both Mos and Hsp70 antibodies. Despite a low-abundance of Mos, the Hsp70 antibody immunoprecipitated Mos as the major protein. Of importance, the Mos protein present in anti-Hsp70 immunoprecipitates functioned as an active MAPKKK indicating that it is not grossly misfolded. It is known that c-Mos protein kinase activity in cell extracts of transfected COS-1 or NIH3T3 cells is labile. We found that the inclusion of adenosine triphosphate (ATP) in cell extracts protected against the loss of Mos kinase activity. In the absence of ATP from cell extracts, protein kinase activity of Mos was lost within 6 h on ice even though the Mos protein was not degraded and remained bound to Hsp70. Based on our identification of c-Mos-Hsp70 interaction, one of the roles of ATP may be to assist the regulation of c-Mos via ATP involvement in the protein-folding function of Hsp70 and possibly other molecular chaperones. We also detected by co-immunoprecipitation a physical association between endogenous c-Mos and Hsp70 in Xenopus eggs. To provide further evidence for the functional significance of Hsp70 interaction to Mos function, we show that the residue serine 3 in Mos, which is important for the regulation of protein kinase activity of Mos is also important for Hsp70 association.

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Acknowledgements

We thank D Toft (Mayo Clinic Foundation, Rochester, MN, USA) for providing the BB70 Hsp70 antibody, RB Arlinghaus for suggestions and critical reading of the manuscript, L Feldman for editorial corrections and L Kimbrough for her help in manuscript preparation. This work was supported by the grants R01 CA45125 and CA16672 (core) from the National Institutes of Health.

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  1. Hui Liu, Vijayalakshmi B Vuyyuru and Chau D Pham: H Liu, VB Vuyyuru and CD Pham contributed equally to this work

Authors and Affiliations

  1. Department of Molecular Pathology, Box 172, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, Texas, USA

    Hui Liu, Vijayalakshmi B Vuyyuru, Chau D Pham, Yandan Yang & Balraj Singh

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  1. Hui Liu
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Liu, H., Vuyyuru, V., Pham, C. et al. Evidence of an interaction between Mos and Hsp70: a role of the Mos residue serine 3 in mediating Hsp70 association. Oncogene 18, 3461–3470 (1999). https://doi.org/10.1038/sj.onc.1202699

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