title: Drak2 is not required for tumor surveillance and suppression.
abstract: Drak2 is a promising therapeutic target to treat organ-specific autoimmune diseases such as type 1 diabetes and multiple sclerosis without causing generalized immune suppression. Inhibition of Drak2 may also prevent graft rejection following organ transplantation. However, Drak2 may function as a critical tumor suppressor, which would challenge the prospect of targeting Drak2 for therapeutic treatment. Thus, we examined the susceptibility of Drak2 (-/-) mice in several tumor models. We show that Drak2 is not required to prevent tumor formation in a variety of settings. Therefore, Drak2 does not function as an essential tumor suppressor in in vivo tumor models. These data further validate Drak2 as a viable therapeutic target to treat autoimmune disease and graft rejection. Importantly, these data also indicate that while Drak2 may induce apoptosis when overexpressed in cell lines, it is not an essential tumor suppressor.
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 351, Memphis, TN 38105, USA.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Edwards
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 351, Memphis, TN 38105, USA.
authors.forename: Tarsha L
authors.initials: TL
authors.lastname: Harris
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 351, Memphis, TN 38105, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Floersh
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 351, Memphis, TN 38105, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Lukens
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 351, Memphis, TN 38105, USA.
authors.forename: Md Hasan
authors.initials: MH
authors.lastname: Zaki
authors.affiliation: Department of Veterinary Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Vogel
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 351, Memphis, TN 38105, USA.
authors.forename: Thirumala-Devi
authors.initials: TD
authors.lastname: Kanneganti
authors.affiliation: Department of Pathology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Jack D
authors.initials: JD
authors.lastname: Bui
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 351, Memphis, TN 38105, USA maureen.mcgargill@stjude.org.
authors.forename: Maureen A
authors.initials: MA
authors.lastname: McGargill
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007157:Immunologic Surveillance; D007165:Immunosuppression Therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000188:drug therapy*; D016377:Organ Transplantation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012509:Sarcoma / Q000188:drug therapy / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D025521:Tumor Suppressor Proteins; C495197:Drak2 protein, mouse; D017346:Protein Serine-Threonine Kinases
keywords: autoimmunity; regulation of immune responses; tumor surveillance