Menin Induces Apoptosis in Murine Embryonic Fibroblasts

Robert W. Schnepp, Hua Mao, Stephen M. Sykes, Wei Xing Zong, Albert Silva, Ping La, Xianxin Hua

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Abstract

Multiple endocrine neoplasia type I (MEN1) is a hereditary tumor syndrome characterized by multiple endocrine and occasionally non-endocrine tumors. The tumor suppressor gene Menl, which is frequently mutated in MEN1 patients, encodes the nuclear protein menin. Although many tumor suppressor genes are involved in the regulation of apoptosis, it is unclear whether menin facilitates apoptosis. Here we show that ectopic overexpression of menin via adenoviruses induces apoptosis in murine embryonic fibroblasts. The induction of apoptosis depends on Bax and Bak, two proapoptotic proteins. Moreover, loss of menin expression compromises apoptosis induced by UV irradiation and tumor necrosis factor-α (TNF-α), whereas complementation of menin-null cells with menin restores sensitivity to UV- and TNF-α-induced apoptosis. Interestingly, loss of menin reduces the expression of procaspase 8, a critical protease that is essential for apoptosis induced by death-related receptors, whereas complementation of the menin-null cells up-regulates the expression of procaspase 8. Furthermore, complementation of menin-null cells with menin increases the activation of caspase 8 in response to TNF-α treatment. These results suggest a proapoptotic function for menin that may be important in suppressing the development of MEN1.

Original languageEnglish (US)
Pages (from-to)10685-10691
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number11
DOIs
StatePublished - Mar 12 2004

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Schnepp, R. W., Mao, H., Sykes, S. M., Zong, W. X., Silva, A., La, P., & Hua, X. (2004). Menin Induces Apoptosis in Murine Embryonic Fibroblasts. Journal of Biological Chemistry, 279(11), 10685-10691. https://doi.org/10.1074/jbc.M308073200