Details

Autor(en) / Beteiligte

• Milne, Thomas A.
• Hughes, Christina M.
• Lloyd, Ricardo
• Yang, Zhaohai
• Rozenblatt-Rosen, Orit
• Dou, Yali
• Schnepp, Robert W.
• Krankel, Cynthia
• LiVolsi, Virginia A.
• Gibbs, Denise
• Hua, Xianxin
• Roeder, Robert G.
• Meyerson, Matthew
• Hess, Jay L.

Titel

Menin and MLL Cooperatively Regulate Expression of Cyclin-Dependent Kinase Inhibitors

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2005-01, Vol.102 (3), p.749-754

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2005

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 p27Kip1and p18Ink4c. Menin activates transcription by means of a mechanism involving recruitment of MLL to the p27Kip1and p18Ink4cpromoters and coding regions. Loss of function of either MLL or menin results in down-regulation of p27Kip1and p18Ink4cexpression 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.