کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2036754 1072280 2009 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The Tumor Suppressor Par-4 Activates an Extrinsic Pathway for Apoptosis
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوشیمی، ژنتیک و زیست شناسی مولکولی (عمومی)
پیش نمایش صفحه اول مقاله
The Tumor Suppressor Par-4 Activates an Extrinsic Pathway for Apoptosis
چکیده انگلیسی

SummaryProstate apoptosis response-4 (Par-4) is a proapoptotic protein with intracellular functions in the cytoplasm and nucleus. Unexpectedly, we noted Par-4 protein is spontaneously secreted by normal and cancer cells in culture, and by Par-4 transgenic mice that are resistant to spontaneous tumors. Short exposure to endoplasmic reticulum (ER) stress-inducing agents further increased cellular secretion of Par-4 by a brefeldin A-sensitive pathway. Secretion occurred independently of caspase activation and apoptosis. Interestingly, extracellular Par-4 induced apoptosis by binding to the stress response protein, glucose-regulated protein-78 (GRP78), expressed at the surface of cancer cells. The interaction of extracellular Par-4 and cell surface GRP78 led to apoptosis via ER stress and activation of the FADD/caspase-8/caspase-3 pathway. Moreover, apoptosis inducible by TRAIL, which also exerts cancer cell-specific effects, is dependent on extracellular Par-4 signaling via cell surface GRP78. Thus, Par-4 activates an extrinsic pathway involving cell surface GRP78 receptor for induction of apoptosis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 138, Issue 2, 23 July 2009, Pages 377–388
نویسندگان
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