Defective anchoring of JNK1 in the cytoplasm by MKK7 in Jurkat cells is associated with resistance to Fas-mediated apoptosis

نویسندگان

  • Jing Wang
  • Ruihong Tang
  • Ming Lv
  • Qingyang Wang
  • Xueying Zhang
  • Yuanyuan Guo
  • Hong Chang
  • Chunxia Qiao
  • He Xiao
  • Xinying Li
  • Yan Li
  • Beifen Shen
  • Jiyan Zhang
چکیده

The c-Jun N-terminal protein kinase (JNK) plays a context-dependent role in tumorigenesis. Stress-induced redistribution of JNK from the cytoplasm to the nucleus has been demonstrated as essential for stress-induced cell death. However, accumulation of basal JNK activity in the nucleus has frequently been seen in tumor cells. Our previous report revealed aberrant nuclear entry of JNK protein in Jurkat human leukemic T-cells even without JNK hyperactivation. Because inhibition of JNK activity, especially JNK1 activity, in Jurkat cells results in augmented Fas-mediated apoptosis, it is possible that aberrant subcellular localization of JNK, especially the JNK1 isoform, contributes to the resistance to Fas-mediated apoptosis. Here we report that MKK7 works as a cytoplasmic anchoring protein for JNK1 in various types of cells, including human peripheral blood mononuclear cell (PBMC) T-cells, but exhibits aberrant nuclear entry in Jurkat cells. Ectopic expression of a JNK1 mutant defective of nuclear entry or a nuclear JNK inhibitor leads to impaired UV-induced apoptosis in both PBMC T- and Jurkat cells. The same treatment shows no effect on Fas-mediated apoptosis of PBMC T-cells but sensitizes Jurkat cells to Fas-mediated apoptosis. Taken together, our work suggests that aberrant subcellular organization of the JNK pathway might render certain tumor cells resistant to Fas-mediated apoptosis.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Basal c-Jun NH2-terminal protein kinase activity is essential for survival and proliferation of T-cell acute lymphoblastic leukemia cells.

Hyperactivation of c-Jun NH2-terminal protein kinase (JNK) has been found in various malignant lymphocytes and inhibition of JNK activity leads to cell cycle arrest and apoptosis. However, the role of JNK activity in the oncogenic growth of T-cell acute lymphoblastic leukemia (T-ALL) cells remains largely unknown. Here, we report that treatment of T-ALL cells with JNK inhibitors led to cell cyc...

متن کامل

Opium induces apoptosis in Jurkat cells via promotion of pro-apoptotic and inhibition of anti-apoptotic molecules

Objective(s): The aim of this study was to determine the important molecules involved in apoptosis induction by opium in Jurkat cell line. Materials and Methods: Jurkat cells were incubated 48 hrs with2.86×10-5 g/ml concentration of opium and apoptosis as well as expression levels of related molecules weremeasured. Results: Our results demonstrated that 50.3±0.2 percent of opium treated Jurka...

متن کامل

Aqueous Humor Levels of Soluble Fas and Fas-ligand in Patients with Primary Open Angle and Pseudoex-foliation Glaucoma

Background: Glaucoma is one of the most common causes of blindness and is usually associated with elevated intraocular pressure. In patients with primary open angle glau-coma the number of trabecular meshwork cells is decreased. Death of the trabecular meshwork cells may be a result of apoptosis. Objective: To investigate the aqueous humor levels of soluble Fas (sFas) and Fas-Ligand (sFasL) in ...

متن کامل

Activation-Induced Apoptosis in T cells: Effect of Age and Caloric Restriction

We have previously shown that the proliferative response of T cells to antigenic or mitogenic stimulus decreased with age and that caloric resection (CR) attenuated the age-related decline in proliferation and IL-2 expression. Because activation-induced apoptosis is known to regulate cell proliferation and eliminate the high number of activated cells during an immune response, it was of interes...

متن کامل

Mcl-1 Is Up Regulated by Prenylated Coumarin, Umbelliprenin in Jurkat Cells

Chronic lymphocytic leukaemia (CLL) is the most common B-cell malignancy in the western world and exists as subtypes with very different clinical courses. Myeloid cell leukemia 1 (Mcl-1) is one member of Bcl-2 family proteins that has been shown to be expressed in various tissues and malignant cells, including CLL, where its expression is significantly associated with a failure to achieve compl...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 22  شماره 

صفحات  -

تاریخ انتشار 2011