title: Small GTPase RBJ mediates nuclear entrapment of MEK1/MEK2 in tumor progression.
abstract: Ras-related small GTPases play important roles in cancer. However, the roles of RBJ, a representative of the sixth subfamily of Ras-related small GTPases, in tumorigenesis and tumor progression remain unknown. Here, we report that RBJ is dysregulated in human gastrointestinal cancers and can promote carcinogenesis and tumor progression via nuclear entrapment of mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)1/MEK2 and activation of ERK1/ERK2. Nucleus-localized RBJ interacts with MEK/ERK and prolongs the duration of MEK/ERK activation. Rbj deficiency abrogates nuclear accumulation of MEK1/MEK2, attenuates ERK1/ERK2 activation, and impairs AOM/DSS-induced colonic carcinogenesis. Moreover, Rbj knockdown inhibits growth of established tumors. Our data suggest that RBJ may be an oncogenic Ras-related small GTPase mediating nuclear accumulation of active MEK1/MEK2 in tumor progression.
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China; National Key Laboratory of Medical Molecular Biology and Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Taoyong
authors.initials: T
authors.lastname: Chen
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China; National Key Laboratory of Medical Molecular Biology and Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Mingjin
authors.initials: M
authors.lastname: Yang
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Songqing
authors.initials: S
authors.lastname: Tang
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Zhu
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Zhang
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Hou
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Liu
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Han
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Qiuyan
authors.initials: Q
authors.lastname: Liu
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Qian
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wan
authors.affiliation: Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
authors.forename: Long
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Zheng
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China; National Key Laboratory of Medical Molecular Biology and Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China; Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address: caoxt@immunol.org.
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
mesh_terms: D016475:3T3 Cells; D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D005770:Gastrointestinal Neoplasms / Q000235:genetics / Q000473:pathology; D015870:Gene Expression; D050956:HSP40 Heat-Shock Proteins; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000378:metabolism*; D048370:MAP Kinase Kinase 2 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D008969:Molecular Sequence Data; D034622:RNA Interference; D034741:RNA, Small Interfering; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D050956:HSP40 Heat-Shock Proteins; D034741:RNA, Small Interfering; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C000589559:DNAJC27 protein, human; D020558:GTP Phosphohydrolases; C000589560:RBJ protein, mouse; D020691:rab GTP-Binding Proteins