The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Menin and MLL cooperatively regulate expression of cyclin-dependent kinase inhibitors
Open accessAbstract
Mutations in the MEN1 gene are associated with the multiple endocrine neoplasia syndrome type 1 (MEN1), which is characterized by parathyroid hyperplasia and tumors of the pituitary and pancreatic islets. The mechanism by which MEN1 acts as a tumor suppressor is unclear. We have recently shown that menin, the MEN1 protein product, interacts with mixed lineage leukemia (MLL) family proteins in a histone methyltransferase complex including Ash2, Rbbp5, and WDR5. Here, we show that menin directly regulates expression of the cyclin-dependent kinase inhibitors p27 Kip1 and p18 Ink4c . Menin activates transcription by means of a mechanism involving recruitment of MLL to the p27 Kip1 and p18 Ink4c promoters and coding regions. Loss of function of either MLL or menin results in down-regulation of p27 Kip1 and p18 Ink4c expression and deregulated cell growth. These findings suggest that regulation of cyclin-dependent kinase inhibitor transcription by cooperative interaction between menin and MLL plays a central role in menin's activity as a tumor suppressor.
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Cites
Bmi1, stem cells, and senescence regulation
Park, I.-K., Morrison, S. J., & Clarke, M. F. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200420800 · Cited by 495
Cited by
Yokoyama, A., Somervaille, T. C. P., Smith, K. S., Rozenblatt-Rosen, O., Meyerson, M., & Cleary, M. L. (2005) · Cell · doi:10.1016/j.cell.2005.09.025 · Cited by 688
Self-citationMenin Critically Links MLL Proteins with LEDGF on Cancer-Associated Target Genes
Yokoyama, A., & Cleary, M. L. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.05.003 · Cited by 555
Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia
Grembecka, J., He, S., Shi, A., Purohit, T., Muntean, A. G., Sorenson, R. J., Showalter, H. D., Murai, M. J., Belcher, A. M., Hartley, T., et al. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.773 · Cited by 462
Self-citationPax7 activates myogenic genes by recruitment of a histone methyltransferase complex
McKinnell, I. W., Ishibashi, J., Le Grand, F., Punch, V. G. J., Addicks, G. C., Greenblatt, J. F., Dilworth, F. J., & Rudnicki, M. A. (2008) · Nature Cell Biology · doi:10.1038/ncb1671 · Cited by 380
Karnik, S. K., Chen, H., McLean, G. W., Heit, J. J., Gu, X., Zhang, A. Y., Fontaine, M., Yen, M. H., & Kim, S. K. (2007) · Science · doi:10.1126/science.1146812 · Cited by 353
Metadata
- Authors
- Milne, T. A., Hughes, C. M., Lloyd, R., Yang, Z., Rozenblatt-Rosen, O., Dou, Y., Schnepp, R. W., Krankel, C., LiVolsi, V. A., Gibbs, D., Hua, X., Roeder, R. G., Meyerson, M., & Hess, J. L.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2005-01-07
- Volume
- 102
- Issue
- 3
- Pages
- 749-754
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2116229314
- Cited by
- 469
- References
- 1
- FWCI
- 22.03
- Type
- journal article
- Language
- en
- Open access
- green
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- Milne, T. A., Hughes, C. M., Lloyd, R., Yang, Z., Rozenblatt-Rosen, O., Dou, Y., Schnepp, R. W., Krankel, C., LiVolsi, V. A., Gibbs, D., Hua, X., Roeder, R. G., Meyerson, M., & Hess, J. L. (2005). Menin and MLL cooperatively regulate expression of cyclin-dependent kinase inhibitors. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0408836102
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