Apoptosis and tumor resistance conferred by Par-4.
Par-4 is a tumor suppressor protein with a pro-apoptotic function. Epigenetic silencing of Par-4 is seen in diverse tumors and Par-4 knockout mice develop spontaneous tumors in various tissues. Endogenous Par-4 is essential for sensitization of cells to diverse apoptotic stimuli, whereas ectopic expression of Par-4 can selectively induce apoptosis in cancer cells. The cancer-specific pro-apoptotic action of Par-4 resides in its centrally located SAC domain. This review emphasizes the role of Par-4/SAC in apoptosis and tumor resistance. SAC transgenic mice display normal development and life span, and, most importantly, are resistant to spontaneous, as well as oncogene-induced, autochthonous tumors. The tumor resistant phenotype and undetectable toxicity of SAC in vivo suggests the SAC domain possesses tremendous therapeutic potential.
Department of Radiation Medicine, University of Kentucky, Lexington, Kentucky 40536, USA.
Yanming
Y
Zhao
Vivek M
VM
Rangnekar
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002645:Chickens / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics*; D002679:Pan troglodytes / Q000235:genetics; D010766:Phosphorylation; D018179:Receptors, Thrombin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis / Q000235:genetics; D015027:Zebrafish / Q000235:genetics
D018179:Receptors, Thrombin; C112908:protease-activated receptor 4