Identification of an in vivo MEK/WOX1 complex as a master switch for apoptosis in t cell leukemia

Hsin Ping Lin, Jean Yun Chang, Sing Ru Lin, Ming Hui Lee, Shenq Shyang Huang, Li Jin Hsu, Nan Shan Chang

研究成果: Article

24 引文 斯高帕斯(Scopus)

摘要

Not all leukemia T cells are susceptible to high levels of phorbol myristate acetate (PMA)-mediated apoptosis. At micromolar levels, PMA induces apoptosis of Jurkat T cells by causing mitochondrial polarization/de-polarization, release of cytosolic granules, and DNA fragmentation. Chemical inhibitors U0126 and PD98059 block mitogen-activated protein kinase kinase 1 (MEK1)-mediated phosphorylation of extracellular signal-regulated kinase (ERK) and prevent apoptosis. Mechanistically, proapoptotic tumor suppressor WOX1 (also named WWOX or FOR) physically interacts with MEK1, in part, in the lysosomes in Jurkat cells. PMA induces the dissociation, which leads to relocation of MEK1 to lipid rafts and WOX1 to the mitochondria for causing apoptosis. U0126 inhibits PMA-induced dissociation of WOX1/MEK1 complex and supports survival of Jurkat cells. In contrast, less differentiated Molt-4 T cells are resistant to PMA-induced dissociation of the WOX1/MEK1 complex and thereby are refractory to apoptosis. U0126 overturns the resistance for enhancing apoptosis in Molt-4 cells. Together, the in vivo MEK1/WOX1 complex is a master on/off switch for apoptosis in leukemia T cells.

原文English
頁(從 - 到)550-562
頁數13
期刊Genes and Cancer
2
發行號5
DOIs
出版狀態Published - 2011 五月 1

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cancer Research

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