Abstract
MEN1 is a likely tumor suppressor gene that encodes a novel protein, menin. Menin is a 610 amino-acid residue protein with as yet unknown function(s). We have used tandem affinity purification and mass spectroscopy to isolate and identify proteins associating with menin from cultured HeLa cell extracts. This strategy has resulted in the isolation and identification of nonmuscle myosin type II-A heavy chain (NMHC II-A) as a menin interacting protein. This interaction was confirmed by glutathione-S-transferase pulldown assays, by coimmunoprecipitation, and by actin selection of myosin. We have further identified the amino-terminal region of menin and the head domain of NMHC II-A to be regions required for this interaction. Moreover menin was seen to colocalize with this myosin isoform in the cleavage furrow of dividing cells by indirect immunofluoresence. These data indicate that menin through binding to NMHC II-A could participate in cell division and in other processes that involve NMHC II-A.
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Acknowledgements
We are greatly indebted to many people who assisted in the course of this work. Many thanks go to Bernard Seraphin (EMBL Germany) for kindly providing the TAP expression cassette and George Poy for DNA sequencing. We also thank John A Hanover, Allen M Spiegel, and Karen E Sukhodolets for critical reading of the manuscript and helpful suggestions and to Francis S Collins, Brian Oliver, Elizabeth Novotny, and Alison Hickman for useful discussions.
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Obungu, V., Lee Burns, A., Agarwal, S. et al. Menin, a tumor suppressor, associates with nonmuscle myosin II-A heavy chain. Oncogene 22, 6347–6358 (2003). https://doi.org/10.1038/sj.onc.1206658
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DOI: https://doi.org/10.1038/sj.onc.1206658
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