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Prostate Apoptosis Response-4 (Par-4) as a Cancer Therapeutic Target
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  • Journal title : Journal of Life Science
  • Volume 25, Issue 8,  2015, pp.947-952
  • Publisher : Korean Society of Life Science
  • DOI : 10.5352/JLS.2015.25.8.947
 Title & Authors
Prostate Apoptosis Response-4 (Par-4) as a Cancer Therapeutic Target
Woo, Seon Min; Kwon, Taeg Kyu;
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Prostate apoptosis response-4 (Par-4) was originally identified in androgen-independent prostate cancer cells undergoing apoptosis. Par-4 is ubiquitously expressed in normal cells and tissues, but it is downregulated in several types of cancers. Par-4 is a 38 kDa tumor suppressor protein encoded by the PARW gene. Par-4 promotes apoptosis in a variety of cancerous cells, but not in normal cells. In this review, we focused on the structure, expression and function of Par-4 in apoptotic signaling pathway. Functional domains of Par-4 include two nuclear localization sequences (NLS), a leucine zipper (LZ) domain, a nuclear export sequence (NES) and selective for apoptosis in cancer cell (SAC) domain. Many studies have underlined the importance of Par-4 in preventing cancer development. The activity of Par-4 is differently regulated by localization of intracellular and extracellular Par-4. Intracellular Par-4 inhibits Akt- and NF-κB-mediated cell survival pathways and downregulates Bcl-2 expression. Extracellular Par-4 activates the extrinsic apoptotic pathway by binding to cell surface receptor GRP78, a stress response protein that is in the endoplasmic reticulum (ER). Endogenous Par-4 sensitizes cancer cells to various apoptotic stimuli, while exogenous Par-4 enhances SAC domain-dependent apoptosis in cancer cells, but not normal cells. Therefore, Par-4 is an attractive target for cancer therapy.
Apoptosis;cancer;prostate apoptosis response-4 (Par-4);nuclear factor-κB (NF-κB);selective for apoptosis in cancer cell (SAC) domain;
 Cited by
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