The tumor suppressor protein menin inhibits AKT activation by regulating its cellular localization

Yan Wang, Atsushi Ozawa, Shadia Zaman, Nijaguna B. Prasad, Settara C. Chandrasekharappa, Sunita K. Agarwal, Stephen J. Marx

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder associated mainly with tumors of multiple endocrine organs. Mutations in the MEN1 gene that encodes for the menin protein are the predominant cause for hereditary MEN1 syndrome. Though menin is a tumor suppressor, its molecular mechanism of action has not been defined. Here, we report that menin interacts with AKT1 in vitro and in vivo. Menin downregulates the level of active AKT and its kinase activity. Through interaction with AKT1, menin suppresses both AKT1-induced proliferation and antiapoptosis in nonendocrine and endocrine cells. Confocal microscopy analysis revealed that menin regulates AKT1 in part by reducing the translocation of AKT1 from the cytoplasm to the plasma membrane during growth factor stimulation. Our findings may be generalizable to other cancers, insofar as we found that loss of menin expression was also associated with AKT activation in a mouse model of pancreatic islet adenoma. Together, our results suggest menin as an important novel negative regulator of AKT kinase activity.

Original languageEnglish (US)
Pages (from-to)371-382
Number of pages12
JournalCancer Research
Issue number2
StatePublished - Jan 15 2011
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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