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.
Zhao
Yanming
Y
Department of Radiation Medicine, University of Kentucky, Lexington, Kentucky 40536, USA.
Rangnekar
Vivek M
VM
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