title: κB-Ras proteins regulate both NF-κB-dependent inflammation and Ral-dependent proliferation.
abstract: The transformation of cells generally involves multiple genetic lesions that undermine control of both cell death and proliferation. We now report that κB-Ras proteins act as regulators of NF-κB and Ral pathways, which control inflammation/cell death and proliferation, respectively. Cells lacking κB-Ras therefore not only show increased NF-κB activity, which results in increased expression of inflammatory mediators, but also exhibit elevated Ral activity, which leads to enhanced anchorage-independent proliferation (AIP). κB-Ras deficiency consequently leads to significantly increased tumor growth that can be dampened by inhibiting either Ral or NF-κB pathways, revealing the unique tumor-suppressive potential of κB-Ras proteins. Remarkably, numerous human tumors show reduced levels of κB-Ras, and increasing the level of κB-Ras in these tumor cells impairs their ability to undergo AIP, thereby implicating κB-Ras proteins in human disease.
authors.affiliation: Department of Microbiology and Immunology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Oeckinghaus
authors.affiliation: Department of Microbiology and Immunology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Postler
authors.affiliation: Department of Microbiology and Immunology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Rao
authors.affiliation: Department of Microbiology and Immunology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Heike
authors.initials: H
authors.lastname: Schmitt
authors.affiliation: Department of Microbiology and Immunology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Verena
authors.initials: V
authors.lastname: Schmitt
authors.affiliation: Department of Microbiology and Immunology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Yenkel
authors.initials: Y
authors.lastname: Grinberg-Bleyer
authors.affiliation: Department of Microbiology and Immunology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Lars I
authors.initials: LI
authors.lastname: Kühn
authors.affiliation: Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Gruber
authors.affiliation: Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
authors.forename: Gustav E
authors.initials: GE
authors.lastname: Lienhard
authors.affiliation: Department of Microbiology and Immunology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. Electronic address: sg2715@columbia.edu.
authors.forename: Sankar
authors.initials: S
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D020690:GTPase-Activating Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D015854:Up-Regulation; D020725:ral GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D020690:GTPase-Activating Proteins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D020725:ral GTP-Binding Proteins; D018631:ras Proteins