TY - JOUR
T1 - Menin Induces Apoptosis in Murine Embryonic Fibroblasts
AU - Schnepp, Robert W.
AU - Mao, Hua
AU - Sykes, Stephen M.
AU - Zong, Wei Xing
AU - Silva, Albert
AU - La, Ping
AU - Hua, Xianxin
PY - 2004/3/12
Y1 - 2004/3/12
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M308073200
DO - 10.1074/jbc.M308073200
M3 - Article
C2 - 14688275
AN - SCOPUS:1642329104
SN - 0021-9258
VL - 279
SP - 10685
EP - 10691
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 11
ER -