title: Mechanisms of apoptosis by the tumor suppressor Par-4.
abstract: Par-4 is a pro-apoptotic, tumor suppressor protein that induces apoptosis selectively in cancer cells. Endoplasmic reticulum-stress and higher levels of protein kinase A in tumor cells confer the coveted feature of cancer selective response to extracellular and intracellular Par-4, respectively. Recent studies have shown that systemic Par-4 confers resistance to tumor growth in mice, and that tumor-resistance is transferable by bone-marrow transplantation. Moreover, recombinant Par-4 inhibits the growth of tumors in mice. As systemic Par-4 induces apoptosis via cell surface GRP78, strategies that promote GRP78 trafficking to the cell surface are expected sensitize cancer cells to circulating levels of Par-4. This review illustrates the domains and mechanisms by which Par-4 orchestrates the apoptotic process in both cell culture models and in physiological settings.
authors.affiliation: Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536, USA.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Hebbar
authors.forename: Chi
authors.initials: C
authors.lastname: Wang
authors.forename: Vivek M
authors.initials: VM
authors.lastname: Rangnekar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D009369:Neoplasms / Q000378:metabolism; D018179:Receptors, Thrombin / Q000235:genetics / Q000378:metabolism*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse; D018179:Receptors, Thrombin; C112908:protease-activated receptor 4