Mxi1 and mxi1-0 antagonize N-myc function and independently mediate apoptosis in neuroblastoma.
Mxi1 and mxi1-0 antagonize N-myc function and independently mediate apoptosis in neuroblastoma.
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DOI：
10.1016/j.tranon.2015.01.002
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发表时间：
2015-02
影响因子：
5
通讯作者：
Wechsler, Daniel S.
中科院分区：
文献类型：
--
作者：
Erichsen, David A.;Armstrong, Michael B.;Wechsler, Daniel S.
Neuroblastoma (NB) is the third most common malignancy of childhood, and outcomes for children with advanced disease remain poor; amplification of the MYCN gene portends a particularly poor prognosis. Mxi1 antagonizes N-Myc by competing for binding to Max and E-boxes. Unlike N-Myc, Mxi1 mediates transcriptional repression and suppresses cell proliferation. Mxi1 and Mxi1-0 (an alternatively transcribed Mxi1 isoform) share identical Max and DNA binding domains but differ in amino-terminal sequences. Because of the conservation of these critical binding domains, we hypothesized that Mxi1-0 antagonizes N-Myc activity similar to Mxi1. SHEP NB cells and SHEP cells stably transfected with MYCN (SHEP/MYCN) were transiently transfected with vectors containing full-length Mxi1, full-length Mxi1-0, or the common Mxi domain encoded by exons 2 to 6 (ex2-6). After incubation in low serum, parental SHEP/MYCN cell numbers were reduced compared with SHEP cells. Activated caspase-3 staining and DNA fragmentation ELISA confirmed that SHEP/MYCN cells undergo apoptosis in low serum, while SHEP/MYCN cells transfected with Mxi1 or Mxi1-0 do not. However, SHEP/MYCN cells transfected with Mxi1 or Mxi1-0 and grown in normal serum showed proliferation rates similar to SHEP cells. Mxi ex2-6 did not affect cell number in low or normal serum, suggesting that amino terminal domains of Mxi1 and Mxi1-0 are critical for antagonism. In the absence of N-Myc, Mxi1 and Mxi1-0 induce apoptosis independently through the caspase-8–dependent extrinsic pathway, while N-Myc activates the caspase-9–dependent intrinsic pathway. Together, these data indicate that Mxi1 and Mxi1-0 antagonize N-Myc but also independently impact NB cell survival.
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影响因子：
11.4
作者：
BODRUG, SE;WARNER, BJ;ADAMS, JM
通讯作者：
ADAMS, JM
影响因子：
2.6
作者：
Guo, Xiao-Ling;Pan, Ling;Ohno, Ruzo
通讯作者：
Ohno, Ruzo
影响因子：
8.8
作者：
Boult, J. K. R.;Taniere, P.;Tselepis, C.
通讯作者：
Tselepis, C.
影响因子：
64.5
作者：
AMATI, B;BROOKS, MW;LAND, H
通讯作者：
LAND, H
DOI：
10.1073/pnas.93.16.8536
发表时间：
1996-08-06
影响因子：
11.1
作者：
Harper, SE;Qiu, YB;Sharp, PA
通讯作者：
Sharp, PA